Systems and methods for peritoneal dialysis having point of use dialysis fluid preparation using water accumulator and disposable set

ABSTRACT

A peritoneal dialysis system includes a water purifier, a cycler, and a disposable set operable with the cycler. The disposable set includes a pumping cassette including a water inlet port, a heater/mixing container in fluid communication with the pumping cassette, a water accumulator, a first water line segment, and a second water line segment. The first water line segment is in fluid communication with the water inlet port and the water accumulator. Additionally, the second water line segment is in fluid communication with the water accumulator and the water purifier.

PRIORITY

This application is a continuation of U.S. application Ser. No.15/588,235, entitled, “Systems And Methods For Peritoneal DialysisHaving Point of Use Dialysis Fluid Preparation Using Water Accumulatorand Disposable Set”, filed May 5, 2017, which claims priority to U.S.Provisional Application Ser. No. 62/332,617, entitled, “Apparatus forProportioning Fluids II”, filed May 6, 2016; U.S. ProvisionalApplication Ser. No. 62/332,623, entitled, “Apparatus for ProportioningFluids II”, filed May 6, 2016; and U.S. Provisional Application Ser. No.62/332,630, entitled, “Apparatus for Proportioning Fluids III”, filedMay 6, 2016, the entire contents of each of which are incorporatedherein by reference and relied upon.

BACKGROUND

The present invention relates to the field of fluid compounding forpreparing fluids particularly for the treatment of renal insufficiency.More specifically, it relates to an apparatus for the treatment of renalinsufficiency configured for compounding finished fluids from two ormore constituent fluids for use as a kidney dialyzing fluid.

In particular, the invention may be used for preparing fluids forperitoneal dialysis, particularly for preparing fluids on-site (e.g. atpatient's home).

The kidneys fulfil many functions, including the removal of water, theexcretion of catabolites (or waste from the metabolism, for example ureaand creatinine), the regulation of the concentration of the electrolytesin the blood (e.g. sodium, potassium, magnesium, calcium, bicarbonate,phosphate, chloride) and the regulation of the acid/base equilibriumwithin the body, which is obtained in particular by the removal of weakacids (phosphates, monosodium acids) and by the production of ammoniumsalts.

In individuals who have lost the use of their kidneys, since theseexcretion and regulation mechanisms no longer work, the body accumulateswater and waste from the metabolism and exhibits an excess ofelectrolytes, as well as, in general, acidosis, the pH of the bloodplasma shifting downwards, below 7.35 (the blood pH normally varieswithin narrow limits of between 7.35 and 7.45).

In the treatment of patients suffering acute or chronic renalinsufficiency, dialysis therapy is employed. The two general categoriesof dialysis therapy are hemodialysis and peritoneal dialysis.

In hemodialysis, the patient's blood is cleansed by passage through anartificial kidney in an extracorporeal membrane system.

The blood treatment involves extracorporeal circulation through anexchanger having a semipermeable membrane (dialyzer) in which thepatient's blood is circulated on one side of the membrane and a dialysisliquid, comprising the main electrolytes of the blood in concentrationsclose to those in the blood of a healthy subject, is circulated on theother side.

Furthermore, a pressure difference is created between the twocompartments of the dialyzer which are delimited by the semipermeablemembrane, so that a fraction of the plasma fluid passes byultrafiltration through the membrane into the compartment containing thedialysis liquid.

In peritoneal dialysis, dialyzing fluid is infused into the patient'speritoneal cavity. This cavity is lined by the peritoneal membrane whichis highly vascularized. The metabolites are removed from the patient'sblood by diffusion across the peritoneal membrane into the dialyzingfluid. Excess fluid, i.e. water is also removed by osmosis induced by ahypertonic dialyzing fluid.

When an aqueous solution is instilled into the peritoneal cavity, thesolute composition equilibrates with that of plasma water by passivediffusion along electrochemical concentration gradients. In addition theflux of fluid across the peritoneum in response to an osmotic agentmoves solutes in the absence of a concentration gradient, leading to theconcept that solute transport occurs partly by convection or ‘solventdrag’. Removal of excess fluid is achieved by adding to the solutionvarious concentrations of an osmotic agent (usually dextrose).Ultrafiltration continues until the dialysate becomes virtuallyisotonic, after which the rate that fluid is absorbed into thecirculation exceeds that of the ultrafiltration induced bytranscapillary hydrostatic pressure gradient alone. Net solute and waterremoval during peritoneal dialysis have been shown to be reduced bydialysate absorption. Through these two processes, diffusion and osmoticultrafiltration, appropriate quantities of solute metabolites and fluidneed to be removed to maintain the patient's body fluid volumes andcomposition within appropriate limits.

There are various types of peritoneal dialysis therapies, includingcontinuous ambulatory peritoneal dialysis (“CAPD”), automated peritonealdialysis (“APD”), including tidal flow APD, and continuous flowperitoneal dialysis (“CFPD”).

CAPD is a manual dialysis treatment. The patient connects manually animplanted catheter to a drain, allowing spent dialysate fluid to drainfrom the peritoneal cavity. The patient then connects the catheter to abag of fresh dialyzing fluid, infusing fresh dialyzing fluid through thecatheter and into the patient. The patient disconnects the catheter fromthe fresh dialyzing fluid bag and allows the dialyzing fluid to dwellwithin the peritoneal cavity, wherein the transfer of waste, toxins andexcess water takes place. After a dwell period, the patient repeats themanual dialysis procedure, for example, four times per day, eachtreatment lasting about an hour. Manual peritoneal dialysis requires asignificant amount of time and effort from the patient, leaving ampleroom for improvement.

Automated peritoneal dialysis (“APD”) is similar to CAPD in that thedialysis treatment includes drain, fill, and dwell cycles. APD machines,however, perform the cycles automatically, typically while the patientsleeps. APD machines free patients from having to manually perform thetreatment cycles and from having to transport supplies during the day.APD machines connect fluidly to an implanted catheter, to a source orbag of fresh dialyzing fluid and to a fluid drain. APD machines pumpfresh dialyzing fluid from the dialyzing fluid source, through thecatheter, into the patient's peritoneal cavity and allow the dialyzingfluid to dwell within the cavity and the transfer of waste, toxins andexcess water to take place. APD machines pump spent dialysate from theperitoneal cavity, through the catheter, to the drain. As with themanual process, several drain, fill and dwell cycles occur during APD. A“last fill” occurs often at the end of CAPD and APD, which remains inthe peritoneal cavity of the patient until the next treatment.

Both CAPD and APD are batch type systems that send spent dialysis fluidto a drain. Tidal flow systems are modified batch systems. With tidalflow, instead of removing all the fluid from the patient over a longerperiod of time, a portion of the fluid is removed and replaced aftersmaller increments of time.

Continuous flow or CFPD systems clean or regenerate spent dialysateinstead of discarding it. The systems flow fluid into or out of thepatient, through a loop. Dialyzing fluid flows into the peritonealcavity through one catheter lumen and out another catheter lumen. Thefluid exiting the patient passes through a reconstitution device thatremoves waste from the dialysate, e.g., via a urea removal column thatemploys urease to enzymatically convert urea into ammonia. The ammoniais then removed from the dialysate by adsorption prior to reintroductionof the dialyzing fluid into the peritoneal cavity. CFPD systems are morecomplicated typically than batch systems.

CAPD, APD (including tidal flow) and CFPD systems can employ a pumpingcassette. The pumping cassette typically includes a flexible membranethat is moved mechanically to push and pull dialysis fluid out of andinto, respectively, the cassette.

Peritoneal dialysis requires the maintenance of aseptic technique forconnection because of the high risk of peritoneal infection. The risk ofinfection is particularly high due to the high number of exchanges ofdialyzing fluid which the patient is exposed to.

In one form of peritoneal dialysis, an automated cycler is used toinfuse and drain dialyzing fluid. This form of treatment may be doneautomatically at night while the patient sleeps The cycler measures theamount of fluid infused and the amount removed to compute the net fluidremoval. The treatment sequence usually begins with an initial draincycle to empty the peritoneal cavity of spent dialysate. The cycler thenperforms a series of fill, dwell, and drain cycles, typically finishingwith a fill cycle.

Peritoneal dialysis generally requires large volumes of dialyzing fluid.Generally, at each application, or exchange, a given patient will infuse2 to 3 liters of dialyzing fluid into the peritoneal cavity. The fluidis allowed to dwell for approximately 1 to 3 hours, at which time it isdrained out and exchanged for fresh fluid. Generally, four suchexchanges are performed daily. Therefore, approximately 8 to 20 litersof dialyzing fluid is required per day, 7 days a week, 365 days a yearfor each patient.

Dialyzing fluids have traditionally been provided in sealed, heatsterilized form, ready for use. Peritoneal dialysis is typicallyperformed using bags with three different concentration of dextrose. Thebags are being delivered to a patient's home as 1 liter to 6 liter bagswith different dextrose concentrations and a normal daily consumption isaround 8 to 20 liters of fluid.

In light of above, several problems become apparent. Shipping andstorage of the sheer volume of fluids required is space consuming.Additionally, the use of multiple prefilled bags produces wastematerials in the form of empty containers and packaging.

An improved peritoneal dialysis system is needed accordingly.

SUMMARY

The present disclosure sets forth sub-systems, methods and structuresfor an overall peritoneal dialysis (“PD”) system that creates dialysissolution at the point of use, e.g., at the PD machine. PD fluid isdelivered directly to the patient's peritoneal cavity. PD fluidtherefore needs to have a level of sterilization suitable for beingintroduced into the patient's peritoneum. PD dialysis fluid isaccordingly premixed and sterilized typically prior to delivery to thelocation of use, usually the patient's home.

A typical daily patient consumption of PD dialysis fluid is eight totwenty liters. The fluid is provided in sterilized bags of sizes up tosix liters, which are packed into boxes and delivered, e.g., monthly,for use to the patient's home. The boxes of fluid may be cumbersome andheavy for PD patients to handle, and consume a substantial area in aroom of their homes. The bags and boxes also produce a relatively largeamount of waste disposed of on a weekly or monthly basis. The present PDsystem reduces significantly both the amount of dialysis solution storedand handled by PD patients and the amount of waste produced.

The overall system in an embodiment includes three primary components,namely, a PD cycler, a water purifier and a disposable set operatingwith both the cycler and the water purifier. The PD cycler may forexample be an Amia® or HomeChoice® cycler marketed by BaxterInternational Inc. The disposable set in an embodiment includes adisposable cassette operated by the cycler and various tubes andconnectors attached to the cassette. As described in detail below, thedisposable set in an embodiment also includes a heating/mixing containerand a water for peritoneal dialysis (“WFPD”) accumulation container. Thedisposable set additionally includes at least one, and in one preferredembodiment two, concentrate containers that hold ingredients needed toprepare fresh dialysis fluid for treatment. In an embodiment, one of theconcentrate containers holds a glucose solution, while the otherconcentrate container holds a buffer solution. Concentrate lines extendfrom the cassette and the concentrate containers and are mated togethervia concentrate connectors. In one embodiment, the concentrateconnectors for the first concentrate, e.g., glucose, are physicallydifferent than the concentrate connectors for the second concentrate,e.g., buffer, so that the patient or user cannot connect the concentratecontainer line for the first concentrate to the cassette line for thesecond concentrate, and vice versa.

The disposable set in various embodiments also includes at least one,and in one embodiment two sterile sterilizing grade filters placed inseries with each other. The sterile sterilizing grade filters may bepass-through filters with pores having average diameters suitable toproduce sterile fluid, e.g., 0.22 micron, including the capability ofremoving endotoxins, resulting in water quality suitable for PD. Thesterile sterilizing grade filters provide the final stage ofsterilization for the water that is used to mix with the one or moreconcentrate to provide a dialysis fluid suitable for PD.

The overall system includes a water purifier and multiple componentsleading to the water purifier. The multiple components include, forexample, a water softener, a particulate pre-filter, a carbon filter, anion-exchange resin cartridge and a regenerating salts cartridge. Thecomponents are located between the water purifier and a source ofpotable or drinkable water. A bacterial growth inhibiting agentcontainer may also be fluidly connected to the water purifier. The waterpurifier itself includes water purification equipment, such as one ormore reverse osmosis unit, an electrodionization unit (optional), one ormore pump to move water within the water purifier and one or more heaterto heat the water within the water purifier. The water purifier alsoincludes at least one reservoir for holding a quantity of water to bepurified and for mixing with an anti-bacterial growth agent if provided.The water purifier may also include a deaerator for removing air fromthe water being purified. The water purifier may further include oroperate with pretreatment equipment, e.g., a water softener module,connected to the patient's pottable water supply.

The water purifier may in an alternative embodiment include one or moreultrafilter to help bring the water exiting the water purifier to a WFPDlevel. For example, multiple ultrafilters may be provided to bring thewater exiting the water purifier to a WFPD quality level, wherein thesterile sterilizing grade filters discussed above for the disposable setare not needed and accordingly not provided. In another embodiment, thewater purifier includes a single ultrafilter, while the disposable setincludes a single sterilizing filter, the combination of which bringsthe water to a level of sterilization suitable for being delivered tothe patient's peritoneal cavity. In the embodiment in which thedisposable set includes two or more sterile sterilizing grade filters,no ultrafilters are needed in the water purifier. For redundancy,however, it is contemplated to provide one or more ultrafilter in thewater purifier in combination with one or more sterile sterilizing gradefilters in the disposable set.

It is also contemplated for the cycler to command the water purifier toprovide WFPD at a heated temperature. PD is performed with the dialysisfluid heated to body temperature or 35° C. to 37° C. It is accordinglycontemplated to ask the water purifier to deliver water at some elevatedtemperature below 35° C. to 37° C., such as 10° C. to 40° C., moreparticularly in one embodiment 20° C. to 25° C., reducing the heatingburden and heating time at the cycler.

The PD cycler is in one embodiment configured to operate the cassette ofthe disposable set pneumatically. Here, the PD cycler may include one ormore positive pressure tank and one or more negative pressure tank.Electrically actuated solenoid valves are located between the pressuretanks and the disposable cassette. A control unit of the PD cyclerelectrically controls the solenoid valves to selectively allow positiveor negative pneumatic pressure to reach the valves and pump chambers ofthe disposable cassette. Positive pressure is applied to close a valveof the cassette or to perform a pump-out or expel stroke at a pumpchamber of the cassette. Negative pressure on the other hand is appliedto open a valve of the cassette or to perform a pump-in or fill strokeat a pump chamber of the cassette.

The pressures used to operate the disposable cassette, e.g., up to 48.3kPa (7 psig) positive pressure and −34.5 kPa (−5 psig) suction pressure,are typically less than the pressure needed to push purified waterthrough the sterile sterilizing grade filters, which can be on the orderof 138.9 to 275.8 kPa (20 to 40 psig) positive pressure. If the sterilesterilizing grade filters somehow become compromised such that they donot offer their normal flow resistance, leading to the disposablecassette seeing the, e.g., 138.9 to 275.8 kPa (20 to 40 psig) positivepressure from the water purifier for driving purified water through thefilters, problems may arise. In particular, a valve chamber of thedisposable cassette being closed under, e.g., 48.3 kPa (7 psig) positivepressure will be opened by the, e.g., 138.9 to 275.8 kPa (20 to 40 psig)purified water pressure. A pump chamber of the disposable cassette beingclosed in a pump-out stroke under, e.g., 20.7 kPa (3 psig) positivepressure will also be opened from the inside of the cassette by the,e.g., 138.9 to 275.8 kPa (20 to 40 psig) purified water pressure. Thepumping membrane of the disposable cassette would be stuck against theoperating surface of the cycler, and the cycler would be unable toremedy the situation.

The present disclosure sets forth multiple solutions for solving theabove-described problem. In one preferred embodiment, a disposable setwater line having the two sterile filters in series and configured toconnect to the water purifier is provided with a water accumulator,e.g., a three liter bag, connected to the water line between the sterilesterilizing grade filters and the disposable cassette. The bag could bea separate bag or be provided as a single compartment of a twocompartment bag, wherein the other compartment provides a heater/mixingcontainer.

In an embodiment, the water line extends from the sterile sterilizinggrade filters to the water accumulator at an inlet and then from anoutlet of the water accumulator to the disposable cassette, such thatall WFPD (as used herein, water upstream of the sterile sterilizinggrade filters will be termed “purified”, while water downstream from thesterile sterilizing grade filters will be termed water for peritonealdialysis of “WFPD”) is forced to flow through the water accumulator.From a pressure standpoint, the water accumulator decouples the waterpurifier from the disposable cassette. The water purifier is able tosupply water to the water accumulator without affecting the cycler,while the cycler is able to push or pull WFPD to or from theheater/mixing bag of the disposable cassette without affecting the wateraccumulator.

Thus, if the sterile sterilizing grade filters somehow becomecompromised, the water accumulator absorbs the overpressure from thewater purifier, leaving the disposable cassette and cycler unaffected.The water accumulator also provides time for one or more pressure sensorlocated within the water purifier to detect a pressure drop on itsoutlet line and for a control unit of the water purifier operating withthe pressure sensor to shut down its pumps and provide an alarm (at thewater purifier and/or sending a signal for the cycler to alarm)indicating a likely breech in sterilizing filter integrity. The wateraccumulator further provides an additional benefit by allowing the waterpurifier to fill the water accumulator with WFPD during all phases ofoperation by the PD cycler. The PD cycler operates in three phases,typically including a fill phase, a dwell phase, and a drain phase. Thewater accumulator may be refilled during all three phases, namely, whilethe cycler (i) pulls fresh dialysis fluid from the heater/mixing baginto the disposable cassette and pushes the fresh dialysis fluid to thepatient, (ii) dwells, and (iii) pulls used dialysis fluid from thepatient into the disposable cassette and pushes the used dialysis fluidto drain. The accumulator bag may therefore be smaller because it onlyneeds to hold one fill volume's worth of WFPD (usually up to two liters)at a time.

In an embodiment, the control unit of the cycler sends a wired orwireless signal to the water purifier requesting a desired amount ofWFPD, upon receipt of which the water purifier prepares and supplies therequested amount of WFPD to the water accumulator. In an embodiment, thewater purifier delivers the requested amount of WFPD to the wateraccumulator while the cycler is draining used dialysis fluid from thepatient and/or while delivering fresh dialysis fluid to the patient.Then, during the dwell phase, the cycler pulls the WFPD from theaccumulator bag, mixes fresh dialysis fluid (described in detail belowincluding a waffling sequence), and delivers the fresh dialysis fluid tothe heater/mixing bag at the end of the waffling sequence, so that thedisposable cassette is free to perform the upcoming drain.

A further advantage of the accumulator bag is that because theaccumulator bag stores a supply of WFPD, and can do so when convenient,the pressure needed to drive purified water through the sterilesterilizing grade filters and the flowrate needed to provide therequested amount of WFPD may both be lower, such that the sterilesterilizing grade filters may be lower rated pressure and flowrate-wise,and thus be more economical. Lower operating pressure within the waterpurifier also creates less stress on its components, yielding anotheradvantage provided by the water accumulator.

In another embodiment, the water accumulator is not provided. Instead, awater recirculation loop is created, which includes a water lineextending from the water purifier to the disposable cassette and a linemerging with the water line prior to the cassette to run back to thewater purifier, creating a loop. The loop allows for a constant flow ofWFPD to be created, which is maintained at a pressure lower than theoperating pressure of the cycler. The cycler via the disposable cassettemay pull WFPD from the recirculation loop as needed. If the sterilesterilizing grade filters fail, the overpressure is distributedthroughout the loop, lessening the pressure impact on the cassette, andproviding time for one or more pressure sensor in the water purifier todetect a pressure drop in its outlet line upstream of the sterilesterilizing grade filters, and for a control unit of the water purifieroperating with the pressure sensor to shut down its pumps and provide analarm (at the water purifier and/or sending a signal for the cycler toalarm) indicating a likely breech in sterilizing filter integrity.

As mentioned above, the present overall system prepares PD dialysisfluid at the point of use. To do so, the control unit causes the cyclerto operate the disposable cassette to pump precise amounts of WFPD andat least one concentrate, such as a glucose and a buffer concentratetogether for mixing and forming a dialysis fluid having a sterilizationlevel suitable for being delivered to the peritoneal cavity of thepatient. Structures to aid the mixing are discussed below. But evenassuming that the resulting fluid has been mixed homogeneously, it stillneeds to be tested. In one embodiment, the mixed dialysis fluid istested using one or more sensor, e.g., a conductivity sensor. For PD,the doctor typically prescribes a type of dialysis fluid to be used fortreating a particular patient. Different PD dialysis fluids aretypically differentiated by dextrose or glucose levels. For example, theassignee of the present disclosure provides different PD dialysis fluidshaving the following dextrose and glucose levels:

1.5% dextrose monohydrate (or glucose monohydrate)=1.36% anhydrousdextrose (or anhydrous glucose),

2.5% dextrose monohydrate (or glucose monohydrate)=2.27% anhydrousdextrose (or anhydrous glucose), and

4.25% dextrose monohydrate (or glucose monohydrate)=3.86% anhydrousdextrose (or anhydrous glucose). This last dialysis fluid (4.25%dextrose) may have a corresponding and repeatable conductivitymeasurement of 11.64 mS/cm. The 11.64 mS/cm is an example used for thisdescription and has been found via experimentation. The conductivitysetpoint for 4.25% dextrose dialysis fluid may vary based on factorssuch as its chemistry. Thus a resulting look-up table stored at thecontrol unit of the cycler will need to be specific as to not onlydextrose/glucose level, but to other factors such as dialysis fluidchemistry. It should be appreciated however that the other two dialysisfluid types listed above (1.5% dextrose and 2.5% dextrose) will producedifferent corresponding and repeatable conductivity measurements.

It is therefore contemplated to use one or more conductivity cell orsensor to confirm that the point of use dialysis solution has been mixedto the correct proportions. In one embodiment, the conductivity cell islocated in the water purifier, where it may be reused. When the cyclerhas completed its mixing, the cycler sends a sample of the mixture downthe drain line from the disposable cassette to the water purifier, whichis connected to a distal end of the drain line. The sample is pushedpast the one or more conductivity sensor located at the water purifier,which reads the conductivity of the sample. One or more conductivityreading is received by the control unit of the water purifier and either(i) the control unit of the water purifier analyzes the one or morereading, determines a “solution good” or “solution bad” result and sendsthe result wired or wirelessly to the control unit of the cycler, whicheither proceeds with treatment or takes an alternative action or (ii)the control unit of the water purifier sends the one or more reading tothe cycler, which analyzes the one or more reading, determines a“solution good” or “solution bad” result and either proceeds withtreatment or takes an alternative action. The alternative action may beeither one or both of alarming or getting rid of the improperlyproportioned dialysis fluid and trying again to hopefully produce adesired volume of properly mixed dialysis solution before the next fillcycle.

It should be appreciated from above that the present system may providedifferent dextrose or glucose level dialysis fluids for different fillprocedures of the same treatment. Also, the present system may blend aparticular dextrose or glucose level dialysis fluid, which has beenoptimized for the patient instead of having to use one of the standardsdialysis fluids listed above

The drain line may be a relatively long line, for example, over ten feetlong. The longer drain line enables placement of the water purifier inlocation distant from the cycler, thereby reducing any noise from thepurifier at the location where the patient is being treated. A longerdrain line is advantageous in one respect because the end of the drainline is connected to the non-sterile, albeit disinfected, waterpurifier. Nevertheless, a long drain line means a long sample is neededto reach the one or more conductivity sensor within the water purifier.It is therefore contemplated not to pump mixed dialysis fluid all theway along the drain line to the one or more conductivity sensor insidethe water purifier and to instead send only the amount of mixed dialysisfluid necessary to ensure that a proper conductivity sensor reading is,or readings are, taken. The rest of the line is filled using WFPD fromthe water accumulator.

In a configuration in which the water accumulator is used, when thecycler has completed the dialysis fluid preparation, the dialysis fluidresides in the heater/mixing bag. The cycler closes the cassette valveto the heater/mixing bag, opens the cassette valve to the wateraccumulator and pumps enough WFPD down the drain line and to the waterpurifier to ensure that the conductivity sensor is seeing water only,which can be checked by comparing a sensor reading to a conductivityreading expected for water only. Next, the cycler closes the cassettevalve to the water accumulator, opens the cassette valve to theheater/mixing bag and pumps the necessary amount of mixed fluid (toproduce a good reading(s) at the conductivity sensor) from theheater/mixing bag into the drain line. The amount of mixed fluid pumpedwill very likely not reach the conductivity sensor in the waterpurifier, so its reading(s) should not change. Then, the cycler closesthe cassette valve to the heater/mixing bag, opens the cassette valve tothe water accumulator and pumps enough WFPD to the water purifier toensure that the entire amount of mixed dialysis fluid has been pumped tothe sensor, and then an additional amount of WFPD to show in the sensorreadings a clear end to the mixed fluid.

In a configuration in which the water accumulator is not used, the drainline may be merged with the water line just prior to the two linesmating with the disposable cassette. The drain line again runs to aconductivity sensor located inside the water purifier. Here, instead ofthe cycler pumping WFPD to clear the drain line prior to the pumping ofthe mixed fluid slug, the cycler closes the cassette valve to thecombined water and drain line, and the water purifier pumps enough WFPDdown the water line and into the drain line to fully prime the drainline past the one or more conductivity sensor with WFPD. Next, thecycler opens the cassette valve to the heater/mixing bag and pumps thenecessary amount of mixed fluid (to produce a good reading(s) at theconductivity sensor) from the heater/mixing bag into the drain line. Theamount of mixed fluid pumped will again very likely not reach theconductivity sensor in the water purifier, so its reading(s) should notchange. Then, the cycler closes the cassette valve to the heater/mixingbag, and with the cassette valve to the combined water and drain linestill closed, the water purifier pumps enough WFPD through the water anddrain lines to ensure that the entire amount of mixed dialysis fluid hasbeen pumped to the sensor, and then an additional amount of WFPD to showin the sensor readings a clear end to the mixed fluid.

In either configuration above, the mixed fluid will intermingle with thewater at either end within the drain tube, but the majority of the mixedfluid slug between the ends will be pure mixed fluid and provide a truereading. The mixed fluid slug bound on both ends by WFPD provides goodcontrast marking the beginning and end of the mixed fluid readout fromthe one or more conductivity sensor over time. The readout is used todetermine if the mixed fluid has the correct proportion as describedherein.

To reduce the amount of mixed fluid that the conductivity sensor needsto see to produce a true or full reading, an estimating function may beused to estimate the conductivity value of the sensor. The estimatingfunction enables an asymptotic value of the conductivity signal to beestimated instead of having to use the amount of mixed fluid needed toactually reach the sensed asymptotic value. The estimating function may,for example, reduce the amount of mixed fluid needed by twenty-fivepercent.

In one alternative embodiment, the conductivity sensor is placed insideof the cycler instead of the water purifier. Here, in one implementationthe drain line runs in a first section from the cassette to the cycler,past the one or more conductivity sensor inside the cycler, and in asecond section from the cycler to a house or container drain. In anotherimplementation, an additional sample line runs in a first section from asample port of the disposable cassette to the cycler, past the one ormore conductivity sensor inside the cycler, and in a second section ofthe sample line from the cycler to a sample container or bag, e.g.,provided as a separate chamber of a two chamber bag, the other chamberbeing the heater/mixing chamber. In another alternative embodiment, oneor more conductivity probe is placed in the disposable cassette. The oneor more probe mates with a conductivity sensor provided with the cyclerwhen the cassette is installed in the cycler.

The conductivity readings for any of the conductivity sensor embodimentsdiscussed herein may be temperature compensated, and thus a temperaturesensor, e.g., a thermistor or thermocouple, may be provided with any ofthe conductivity sensor embodiments described herein. Also, in any ofthe conductivity sensor embodiments discussed herein, the line leadingto the conductivity sensor, e.g., the drain line or a sample line, mayhave a one-way valve, e.g., a duck-billed check valve, that helps toprevent contaminants from migrating counter-flow up into the disposablecassette.

As discussed herein, mixing is performed at least in part inside theheater/mixing container or bag provided as part of the disposable set.The heater of the cycler is located at the top of the cycler in oneembodiment, so that the heater/mixing bag may simply be placed on top ofthe cycler for treatment. In an embodiment, the cycler includes a lidthat is closed over the heater/mixing bag to help improve heatingefficiency. When the heater/mixing container is filled with fluid, thebag port that transitions the heater/mixing line to the bag itself canbe bent or rotated upwardly such that the port points upwardly towardsthe top of the bag instead of straight out towards the far edge of theheater/mixing bag. In an embodiment, the mixing takes place as follows:the cycler delivers a smaller percentage, such as ten percent, of theprescribed WFPD to the bag, the entire glucose concentrate volume to thebag, the entire buffer concentrate volume to the bag, then theremaining, e.g., ninety, percent of the prescribed WFPD to the bag.Also, the glucose and buffer concentrates are heavier than WFPD. Thus ifthe bag port is rotated upwardly when providing the remaining ninetypercent of the prescribed WFPD, the water can tend to shoot over theheavier concentrates and not mix homogeneously.

To solve this problem, the bag port is provided in one embodiment withfirst and second flanges that extend out from the port and transverselyto the axis of the bag port. When the port is properly mounted into aslot formed in a sidewall of the heater tray located at the top of thecycler, the flanges extend in a sort of semicircle above the top of thebag port. The flanges are spaced apart from each other a distancecorresponding to the wall thickness of the heater tray sidewall, so thatone flange resides on the outside of the heater tray sidewall, while thesecond flange resides on the inside of the heater tray sidewall when theport is properly mounted into the sidewall slot. The flanges accordinglyabut either side of the sidewall and prevent the bag port from beingrotated either up towards the top of the heater/mixing bag or downtowards the bottom of the heater/mixing bag. In an embodiment, a key isprovided between the flanges and extends vertically up the center of theflanges, so that the heater/mixing bag cannot be loaded upside down ontothe heater tray.

It is also contemplated to configure the heater lid to close onto someportion of the bag port, either onto one or both of the flanges and/oronto the tubing portion of the bag port, to clamp the bag port in place.The clamping prevents the bag port from translating upwardly within theslot of the heater tray sidewall while the heater/mixing bag is filled.

In another embodiment, the mixing takes place as follows. A sample ofthe first concentrate is pumped past a conductivity sensor to verifythat it is the correct first concentrate. If so, a desired volume of thefirst concentrate is pumped to the heater/mixing bag. A sample of thesecond concentrate is pumped past the conductivity sensor to verify thatit is the correct second concentrate. If so, a desired volume of thesecond concentrate is pumped to the heater/mixing bag. Next, a largepercentage of the desired volume, e.g., 90 to 95%, of the WFPD is pumpedto the heater/mixing bag to mix with the first and second concentrates.Once mixed, a sample of the mixture is pumped past the conductivitysensor and a reading of its conductivity is taken. The reading iscompared to a desired conductivity level to determine how much more WFPDis needed to reach the desired conductivity level. That amount of WFPDis then pumped to the heater/mixing bag. A sample of the resultingmixture is then pumped past the conductivity sensor to verify that thedesired conductivity level has been reached.

For any of the mixing embodiments discussed herein, to further aid thehomogeneous mixing of the dialysis fluid, the control unit of the cycleris in one embodiment programmed to perform a “waffling” sequence. Thewaffling sequence is performed for example after the remaining ninetypercent of the prescribed WFPD is added to the bag to mix with theconcentrates already in the bag. The disposable cassette is in oneembodiment provided with two pumping chambers, so what while one pumpchamber is filling with a fluid, the other pump chamber can expel fluidto provide a relatively continuous flow of fluid to or from thecassette. The waffling sequence in one embodiment involves the cyclercausing the pump chambers to pull the dialysis fluid to be mixed fromthe heater/mixing bag into the pump chambers and then push the dialysisfluid to be mixed back into the heater/mixing bag. This procedure isrepeated over and over until, for example, 200 percent of theheater/mixing bag volume is pumped back and forth. The pump chambers maybe caused to fill and expel together or to have one pump chamber fill,while the other pump chamber expels. Having one pump chamber fill whilethe other expels might be possible at the same time through a singleheater/mixing line, but if not, having one pump chamber fill while theother expels could be performed at alternating times.

The waffling sequence is performed in one embodiment while the mixingfluid is being heated in the heater/mixing bag. In an embodiment,pumping to the heater/mixing bag is performed at about 24.8 kPa (3.6psig). The electrically operated valves controlling pneumatic pressureto the pump chambers are in one embodiment variable pneumatic valves. Itis accordingly contemplated to vary the input signal to the variablepneumatic valves during the waffling sequence, e.g., in a pulse, cyclicor sinewave like manner, such as 3.5 kPa (0.5 psig) up and down from the24.8 kPa (3.6 psig) pumping pressure. The pulsed pressure output mayfurther promote turbulent flow and thus mixing.

The disposable set including the one or more sterilizing filter isdiscarded after each use in one embodiment. In alternative embodiments,the disposable set including the cassette, associated lines,heater/mixing bag, water accumulator (if provided) and one or moresterilizing filter are reused for one or more additional treatment. Todo so, it is contemplated to flush the disposable cassette with WFPD atthe end of treatment to push residual used dialysis fluid from thecassette and the drain line to drain. The patient disconnects thepatient line from the patient's transfer set (which leads to thepatient's indwelling peritoneal catheter) and caps the transfer set andpatient line each with a cap, e.g., a cap containing a disinfectant. Inan alternative embodiment, the drain line, for example, is provided witha port for connecting to the end of the patient line between treatmentsto create a patient line loop that may be more effectively flushed ordisinfected. The concentrate lines of the cassette are left connected tothe concentrate containers. The water line from the cassette is leftconnected to the water purifier. The drain line from the cassette isleft connected to drain, e.g., via a drain line connection to the waterpurifier having the at least one conductivity sensor as discussedherein.

In an embodiment, the number of times that the disposable set may bereused is keyed off of the level of concentrates in the concentratecontainers. For example, the concentrate containers may be configured tohold and provide three treatment's worth of concentrate (plus some extrato ensure three full treatments). It is therefore intended that thedisposable set be reused two times, so that at the end of threetreatments, the patient may simply remove the disposable set withconcentrate containers connected from the cycler for disposal, andreconnect a new disposable set along with two new concentratecontainers. As discussed herein, however, it is possible that the cyclermay prepare a batch of mixed dialysis fluid whose conductivity readingdoes not meet a designated conductivity (or fall with a designated rangeof conductivities) for the prescribed dextrose or glucose levelconcentrate, such that the batch is thereafter discarded. Here, anamount of concentrate may be consumed so that three full treatments areno longer possible. It is contemplated therefore that the control unitof the cycler keep track of the amount of each concentrate consumed overthe three treatment period so that the control unit may (i) prevent theuser from beginning a treatment when there is not enough of eitherconcentrate to complete the treatment and/or (ii) provide an option tothe user to perform a treatment with one or more less cycles.

In an embodiment, when the user installs a new set with new concentratecontainers, the control unit may know that the concentrate containersare new by (i) input indicating same from the patient or user, (ii)sensing/reading a new barcode, 3d barcode, radio frequency identifier(“RFID”) tag, or other sensed identifier provided with the newconcentrate containers, e.g., provided on a connecter extending from thecontainers, or (iii) a combination of (i) and (ii). When the controlunit of the cycler senses the new containers, the control unit resetsthe amount of each concentrate consumed to zero.

To aid in the reuse of the disposable set, it is contemplated to use asupply of a bacterial growth prevention agent, such as citric acid,citrate, or a derivative thereof. In an embodiment, the supply of thebacterial growth prevention agent is connected as an input to the waterpurifier. The water purifier as a last step at the end of treatmentmixes a desired amount of the bacterial growth prevention agent into thepurified water, which is then brought to a sterilization level suitablefor being delivered to the peritoneal cavity of the patient via thesterile sterilizing grade filters and delivered to the water accumulatorin one embodiment. The cycler in its last step at the end of treatmentpulls WFPD including the growth inhibitor from the water accumulator andpumps the water and inhibitor into and through the cassette, drain lineand possibly even the heater/mixing container. In a further alternativeembodiment, hot water heated at the water purifier, e.g., to 70° C., maybe used to disinfect the disposable set between treatments.

In light of the present disclosure, and without limiting the disclosurein any way, in a first aspect, which may be combined with any otheraspect listed herein unless specified otherwise, a peritoneal dialysissystem includes: a water purifier; a cycler; and a disposable setoperable with the cycler, the disposable set including a pumpingcassette including a water inlet port, a heater/mixing container influid communication with the pumping cassette, a water accumulator, afirst water line segment in fluid communication with the water inletport and the water accumulator, and a second water line segment in fluidcommunication with the water accumulator and the water purifier.

In a second aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the secondwater line segment is provided with at least one sterile sterilizinggrade filter.

In a third aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the waterpurifier is configured to enter an alarm state upon sensing a change inoperating pressure due to failure of the at least one sterilesterilizing grade filter, and wherein the water accumulator ispositioned and arranged to absorb the change in operating pressure.

In a fourth aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the alarmstate includes notification from the water purifier to the cycler.

In a fifth aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the waterpurifier includes an ultrafilter and the disposable set includes asterile sterilizing grade filter.

In a sixth aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the waterpurifier includes a plurality of ultrafilters.

In a seventh aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thefirst water line segment is in fluid communication with an outlet of thewater accumulator and the second water line segment is in fluidcommunication with an inlet of the water accumulator.

In an eighth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, theheater/mixing container and the water accumulator are provided asdifferent chambers of a multi-chamber bag.

In a ninth aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, thedisposable set further includes a drain line, and wherein a distal endof the drain line is configured to be connected to the end of the secondwater line segment connected to the water purifier when removed from thewater purifier.

In a tenth aspect of the present disclosure, which may be combined withany other aspect listed herein unless specified otherwise, the distalend of the drain line is configured to be connected to a connectorlocated at the water purifier.

In an eleventh aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, aperitoneal dialysis system includes: a water purifier; a cyclerincluding a pump actuator; a disposable set operable with the cycler,the disposable set including a pumping cassette including a pump chamberplaceable in operable communication with the pump actuator, aheater/mixing container in fluid communication with the pumpingcassette, and a water accumulator in fluid communication with thepumping cassette and the water purifier, and wherein the system isconfigured to cause the water purifier to pump water purified by thewater purifier towards the water accumulator while (i) the pump actuatoris actuating the pump chamber to pump fresh dialysis fluid from theheater/mixing container during a fill phase, (ii) treatment is in adwell phase, or (iii) the pump actuator is actuating the pump chamber topump used dialysis fluid from the pumping cassette during a drain phase.

In a twelfth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thewater purifier includes a water purifier control unit and the cyclerincludes a cycler control unit, and wherein the cycler control unit isconfigured to command the water purifier control unit to cause the waterpurifier to pump water purified by the water purifier towards the wateraccumulator during (i), (ii) or (iii) set forth in the eleventh aspect.

In a thirteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thecycler control unit is configured to control (i), (ii) and (iii) setforth in the eleventh aspect.

In a fourteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thecycler is configured to cause the pump actuator to actuate the pumpchamber to mix water purified by the water purifier with at least oneconcentrate while treatment is in the dwell phase.

In a fifteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thecycler is configured to cause the pump actuator to actuate the pumpchamber to pull water purified by the water purifier from the wateraccumulator into the pump chamber while treatment is in the dwell phase.

In a sixteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thecycler is configured to cause the pump actuator to actuate the pumpchamber to push water purified by the water purifier to theheater/mixing container while treatment is in the dwell phase.

In a seventeenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, aperitoneal dialysis system includes: a water purifier including a wateroutlet connector, a water recirculation connector, and an internalrecirculation loop from the water outlet connector to the waterrecirculation connector; a cycler; and a disposable set operable withthe cycler, the disposable set including (i) a pumping cassetteincluding a water inlet port, (ii) a water line in fluid communicationwith the water inlet port and the water outlet connector, the water lineincluding at least one sterile sterilizing grade filter, and (iii) arecirculation line in fluid communication with the water line downstreamfrom the sterile sterilizing grade filter and the water recirculationconnector, wherein the recirculation line and the internal recirculationloop absorb pressure upon a failure of the at least one sterilesterilizing grade filter.

In an eighteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thedisposable set of the seventeenth aspect further includes aheater/mixing container in fluid communication with the pumpingcassette.

In a nineteenth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, thewater purifier is configured to enter an alarm state upon sensing achange in operating pressure due to the failure of the at least onesterile sterilizing grade filter, and wherein the recirculation line andthe internal recirculation loop provide time for the water purifier toreact to the change in operating pressure.

In a twentieth aspect of the present disclosure, which may be combinedwith any other aspect listed herein unless specified otherwise, theperitoneal dialysis system includes a pump in operable communicationwith the internal recirculation loop.

In a twenty-first aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a disposable set for operation with first and second concentratecontainers in fluid communication with first and second concentratecontainer connectors is provided, the disposable set including: apumping cassette including a patient line port, a drain line port, awater inlet port, a heater/mixing port, a first concentrate port, and asecond concentrate port; a patient line in fluid communication with thepatient line port; a drain line in fluid communication with the drainline port; a water line in fluid communication with the water line port;a heater/mixing container in fluid communication with the heater/mixingport; a first concentrate line in fluid communication with the firstconcentrate port, the first concentrate line terminating at a firstconcentrate line connector having a first configuration for mating withthe first concentrate container connector; and a second concentrate linein fluid communication with the second concentrate port, the secondconcentrate line terminating at a second concentrate line connectorhaving a second, different configuration for mating with the secondconcentrate container connector, such that (i) the first concentrateline connector cannot mate with the second concentrate containerconnector, and (ii) the second concentrate line connector cannot matewith the first concentrate container connector.

In a twenty-second aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,the first configuration and the second configuration have differentthread sizes.

In a twenty-third aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,the first configuration includes one of the first concentrate lineconnector or the first concentrate container connector having a firstshroud differential between an end of a first shroud and an end of afirst male luer port, wherein the second configuration includes one ofthe second concentrate line connector or the second concentratecontainer connector having a second shroud differential between an endof a second shroud and an end of a second male luer port, and whereinthe second shroud differential is different than the first shrouddifferential.

In a twenty-fourth aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a distal end of the patient line includes a patient line connectorhaving a third configuration for mating with a patient transfer set, thethird configuration different than the first and second configurations.

In a twenty-fifth aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a distal end of the drain line includes a drain line connector having athird configuration for mating with a mating connector, the thirdconfiguration different than the first and second configurations.

In a twenty-sixth aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a distal end of the water line includes a water line connectorconfigured to mate with the drain line connector.

In a twenty-seventh aspect of the present disclosure, which may becombined with any other aspect listed herein unless specified otherwise,a distal end of the water line includes a water line connector having athird configuration for mating with a water purifier, the thirdconfiguration different than the first and second configurations.

In a twenty-eighth aspect of the present disclosure, any of thestructure, functionality and alternatives described in connection withany one of FIGS. 1 to 20 may be used in combination with any of thestructure, functionality and alternatives described in connection withany other ones of FIGS. 1 to 20.

It is accordingly an advantage of the present disclosure to provide animproved peritoneal dialysis system.

It is another advantage of the present disclosure to provide aperitoneal dialysis system that prepares dialysis fluid having asterilization level suitable for being delivered to the peritonealcavity of the patient at the point of use.

It is a further advantage of the present disclosure to provide aperitoneal dialysis system that prepares dialysis fluid having asterilization level suitable for being delivered to the peritonealcavity of the patient at the point of use safely.

It is still a further advantage of the present disclosure to provide aperitoneal dialysis system that mixes dialysis fluid having asterilization level suitable for being delivered to the peritonealcavity of the patient at the point of use effectively.

It is still another advantage of the present disclosure to provide aperitoneal dialysis system that effectively tests the proportionalaccuracy of dialysis fluid made at the point of use.

It is yet a further advantage of the present disclosure to provide aperitoneal dialysis system that allows for the reuse of disposablecomponents.

Further still, it is an advantage of the present disclosure to providedialysis fluids having dextrose or glucose levels optimized for thepatient.

Still further, it is an advantage of the present disclosure to providedialysis fluid treatments that optimally provide different dextrose orglucose level dialysis fluids for different fill procedures of a sametreatment.

Moreover, it is an advantage of the present disclosure to use adisinfection procedure performed routinely at a water purifier betweentreatments to aid in the formation of water suitable for peritonealdialysis at the time of treatment.

The advantages discussed herein may be found in one, or some, andperhaps not all of the embodiments disclosed herein. Additional featuresand advantages are described herein, and will be apparent from, thefollowing Detailed Description and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a front elevation view of one embodiment of a peritonealdialysis system having point of use dialysis fluid production of thepresent disclosure.

FIG. 2 is an elevation view of one embodiment of a disposable set usedwith the system illustrated in FIG. 1.

FIGS. 3A to 3D are various views of one embodiment for concentrateconnectors used with any of the disposable sets of the presentdisclosure including the disposable set of FIG. 2.

FIGS. 4A to 4G illustrate various views of one embodiment of aheater/mixing bag port and associated heater/mixing pan sidewall of thepresent disclosure.

FIG. 5 is a process flow diagram illustrating one dialysis fluid mixing,dialysis fluid testing, and treatment method suitable for use with thesystem illustrated in FIG. 1.

FIG. 6 is a front elevation view of another embodiment of a peritonealdialysis system having point of use dialysis fluid production of thepresent disclosure.

FIG. 7 is a front elevation view of another embodiment of a peritonealdialysis system having point of use dialysis fluid production of thepresent disclosure.

FIG. 8 is a front elevation view of a further embodiment of a peritonealdialysis system having point of use dialysis fluid production of thepresent disclosure.

FIG. 9A is an elevation view of one embodiment of a disposable set usedwith the system illustrated in FIG. 8.

FIG. 9B is an elevation view illustrating the disposable cassette of thedisposable set illustrated in FIG. 9A.

FIG. 10 is a front elevation view of the system of FIG. 8 prior toconcentrate container connection.

FIG. 11 is a front elevation view of the system of FIG. 8 prior to waterpurifier connection.

FIG. 12 is a front elevation view of the system of FIG. 8 having anadditional concentrate and sterile sterilizing grade filters placed inseparate locations along the disposable set.

FIG. 13 is a front elevation view of the system of FIG. 8, but whichuses ultrafilters instead of sterile sterilizing grade filters toproduce water for peritoneal dialysis (“WFPD”).

FIG. 14 is a front elevation view of the system of FIG. 8, but whichuses an ultrafilter in combination with a sterilizing filter at a firstlocation to produce WFPD.

FIG. 15 is a front elevation view of the system of FIG. 8, but whichuses an ultrafilter in combination with a sterilizing filter at a secondlocation to produce WFPD.

FIG. 16 is a schematic view of one embodiment of a water purifier thatmay be used with any of the peritoneal dialysis systems having point ofuse dialysis fluid production discussed herein.

FIGS. 17 to 19 illustrate various plots associated with one embodimentof an estimating algorithm of the present disclosure, which may be usedwith any of the peritoneal dialysis systems having point of use dialysisfluid production discussed herein, wherein the estimating algorithmenables the amount of mixed dialysis fluid needed to obtain a suitableconductivity reading to be lessened.

FIG. 20 illustrates a plot associated with another embodiment of anestimating algorithm of the present disclosure, here showing tested,e.g., dialysis, fluid temperature over time, and which may be used withany of the peritoneal dialysis systems having point of use dialysisfluid production discussed herein, wherein the estimating algorithmenables the amount of mixed dialysis fluid needed to obtain a suitableconductivity reading to be lessened.

DETAILED DESCRIPTION Cycler and Disposable Set

Referring now to the drawings and in particular to FIG. 1, oneembodiment of a peritoneal dialysis system having point of use dialysisfluid production of the present disclosure is illustrated by system 10a. System 10 a includes a cycler 20 and a water purifier 110. Suitablecyclers for cycler 20 include, e.g., the Amia® or HomeChoice® cyclermarketed by Baxter International Inc., with the understanding that thosecyclers need updated programming to perform and use the point of usedialysis fluid produced according to system 10 a. To this end, cycler 20includes a control unit 22 having at least one processor and at leastone memory. Control unit 22 further incudes a wired or wirelesstransceiver for sending information to and receiving information from awater purifier 110. Water purifier 110 also includes a control unit 112having at least one processor and at least one memory. Control unit 112further incudes a wired or wireless transceiver for sending informationto and receiving information from control unit 22 of cycler 20. Wiredcommunication may be via Ethernet connection, for example. Wirelesscommunication may be performed via any of Bluetooth™, WiFi™, Zigbee®,Z-Wave®, wireless Universal Serial Bus (“USB”), or infrared protocols,or via any other suitable wireless communication technology.

Cycler 20 includes a housing 24, which holds equipment programmed viacontrol unit 22 to prepare fresh dialysis solution at the point of use,pump the freshly prepared dialysis fluid to patient P, allow thedialysis fluid to dwell within patient P, then pump used dialysis fluidto a drain. In the illustrated embodiment, water purifier includes adrain line 114 leading to a drain 116, which can be a housing drain ordrain container. The equipment programmed via control unit 22 to preparefresh dialysis solution at the point of use in an embodiment includesequipment for a pneumatic pumping system, including but not limited to(i) one or more positive pressure reservoir, (ii) one or more negativepressure reservoir, (iii) a compressor and a vacuum pump each undercontrol of control unit 22, or a single pump creating both positive andnegative pressure under control of control unit 22, for providingpositive and negative pressure to be stored at the one or more positiveand negative pressure reservoirs, (iv) plural pneumatic valve chambersfor delivering positive and negative pressure to plural fluid valvechambers, (v) plural pneumatic pump chambers for delivering positive andnegative pressure to plural fluid pump chambers, (vi) pluralelectrically actuated on/off solenoid pneumatic valves under control ofcontrol unit 22 located between the plural pneumatic valve chambers andthe plural fluid valve chambers, (vii) plural electrically actuatedvariable orifice pneumatic valves under control of control unit 22located between the plural pneumatic pump chambers and the plural fluidpump chambers, (viii) a heater under control of control unit 22 forheating the dialysis fluid as it is being mixed in one embodiment, and(viii) an occluder 26 under control of control unit 22 for closing thepatient and drain lines in alarm and other situations.

In one embodiment, the plural pneumatic valve chambers and the pluralpneumatic pump chambers are located on a front face or surface ofhousing 24 of cycler 20. The heater is located inside housing 24 and inan embodiment includes heating coils that contact a heating pan, whichis located at the top of housing 24, beneath a heating lid (not seen inFIG. 1).

Cycler 20 in the illustrated embodiment includes a user interface 30.Control unit 22 in an embodiment includes a video controller, which mayhave its own processing and memory for interacting with primary controlprocessing and memory of control unit 22. User interface 30 includes avideo monitor 32, which may operate with a touch screen overlay placedonto video monitor 32 for inputting commands via user interface 30 intocontrol unit 22. User interface 30 may also include one or moreelectromechanical input device, such as a membrane switch or otherbutton. Control unit 22 may further include an audio controller forplaying sound files, such as voice activation commands, at one or morespeaker 34.

Water purifier 110 in the illustrated embodiment also includes a userinterface 120. Control unit 112 of water purifier 110 in an embodimentincludes a video controller, which may have its own processing andmemory for interacting with primary control processing and memory ofcontrol unit 112. User interface 120 includes a video monitor 122, whichmay likewise operate with a touch screen overlay placed onto videomonitor 122 for inputting commands into control unit 112. User interface120 may also include one or more electromechanical input device, such asa membrane switch or other button. Control unit 112 may further includean audio controller for playing sound files, such as alarm or alertsounds, at one or more speaker 124 of water purifier 110.

Referring additionally to FIG. 2, one embodiment of disposable set 40illustrated. Disposable set 40 is also illustrated in FIG. 1, mated tocycler 20 to move fluid within the disposable set 40, e.g., to mixdialysis fluid as discussed herein. Disposable set 40 in the illustratedembodiment includes a disposable cassette 42, which may include a planarrigid plastic piece covered on one or both sides by a flexible membrane.The membrane pressed against housing 24 of cycler 20 forms a pumping andvalving membrane. FIG. 2 illustrates that disposable cassette 42includes fluid pump chambers 44 that operate with the pneumatic pumpchambers located at housing 24 of cycler 20 and fluid valve chambers 46that operate with the pneumatic valve chambers located at housing 24 ofcycler 20.

FIGS. 1 and 2 illustrate that disposable set 40 includes a patient line50 that extends from a patient line port of cassette 42 and terminatesat a patient line connector 52. FIG. 1 illustrates that patient lineconnector 52 connects to a patient transfer set 54, which in turnconnects to an indwelling catheter located in the peritoneal cavity ofpatient P. Disposable set 40 includes a drain line 56 that extends froma drain line port of cassette 42 and terminates at a drain lineconnector 58. FIG. 1 illustrates that drain line connector 58 connectsremoveably to a drain connector 118 of water purifier 110.

FIGS. 1 and 2 further illustrate that disposable set 40 includes aheater/mixing line 60 that extends from a heater/mixing line port ofcassette 42 and terminates at a heater/mixing bag 62 discussed in moredetail below. Disposable set 40 includes an upstream water line segment64 a that extends to a water inlet 66 a of water accumulator 66. Adownstream water line segment 64 b extends from a water outlet 66 b ofwater accumulator 66 to cassette 42. In the illustrated embodiment,upstream water line segment 64 a begins at a water line connector 68 andis located upstream from water accumulator 66. FIG. 1 illustrates thatwater line connector 68 is removeably connected to a water outletconnector 128 of water purifier 110.

Water purifier 110 outputs water and possibly water suitable forperitoneal dialysis (“WFPD”). To ensure WFPD, however, a sterilesterilizing grade filter 70 a is placed upstream from a downstreamsterile sterilizing grade filter 70 b, respectively. Filters 70 a and 70b may be placed in water line segment 64 a upstream of water accumulator66. Sterile sterilizing grade filters 70 a and 70 b may be pass-throughfilters that do not have a reject line. Pore sizes for sterilizingfilter may, for example, be less than a micron, such as 0.1 or 0.2micron. Suitable sterile sterilizing grade filters 70 a and 70 b may,for example, be Pall IV-5 or GVS Speedflow filters, or be filtersprovided by the assignee of the present disclosure. In an embodiment,only one upstream or downstream sterilizing filter 70 a and 70 b isneeded to produce WFPD, that is, water suitable for making dialysisfluid for delivery to the peritoneal cavity of patient P, nevertheless,two sterile sterilizing grade filters 70 a and 70 b are provided forredundancy in case one fails.

FIG. 2 further illustrates that a last bag or sample line 72 may beprovided that extends from a last bag or sample port of cassette 42.Last bag or sample line 72 terminates at a connector 74, which may beconnected to a mating connector of a premixed last fill bag of dialysisfluid or to a sample bag or other sample collecting container. Last bagor sample line 72 and connector 74 may be used alternatively for a thirdtype of concentrate if desired.

FIGS. 1 and 2 illustrate that disposable set 40 includes a first, e.g.,glucose, concentrate line 76 extending from a first concentrate port ofcassette 42 and terminates at a first, e.g., glucose, cassetteconcentrate connector 80 a. A second, e.g., buffer, concentrate line 78extends from a second concentrate port of cassette 42 and terminates ata second, e.g., buffer, cassette concentrate connector 82 a.

FIG. 1 illustrates that a first concentrate container 84 a holds afirst, e.g., glucose, concentrate, which is pumped from container 84 athrough a container line 86 to a first container concentrate connector80 b, which mates with first cassette concentrate connector 80 a. Asecond concentrate container 84 b holds a second, e.g., buffer,concentrate, which is pumped from container 84 b through a containerline 88 to a second container concentrate connector 82 b, which mateswith second cassette concentrate connector 82 a.

In an embodiment, to begin treatment, patient P loads cassette 42 intocycler and in a random or designated order (i) places heater/mixing bag62 onto cycler 20, (ii) connects upstream water line segment 64 a towater outlet connector 128 of water purifier 110, (iii) connects drainline 56 to drain connector 118 of water purifier 110, (iv) connectsfirst cassette concentrate connector 80 a to first container concentrateconnector 80 b, and (v) connects second cassette concentrate connector82 a to second container concentrate connector 82 b. At this point,patient connector 52 is still capped. Once fresh dialysis fluid isprepared and verified as described in detail below, patient line 50 isprimed with fresh dialysis fluid, after which patient P may connectpatient line connector 52 to transfer set 54 for treatment. Each of theabove steps may be illustrated graphically at video monitor 32 and/or beprovided via voice guidance from speakers 34.

For disposable set 40, the rigid portion of cassette 42 may be made forexample of a thermal olefin polymer of amorphous structure (“TOPAS”)cyclic olefin copolymer (“coc”). The flexible membranes of cassette 42may be made for example of a copolyletser ether (“PCCE”) and may be ofone or more layer. Any of the tubing or lines may be made for example ofpolyvinyl chloride (“PVC”). Any of the connectors may be made forexample of acrylonitrile-butadiene-styrene (“ABS”, e.g., for concentrateconnectors 80 a, 80 b, 82 a, 82 b and heater/mixing bag connector 100discussed below), acrylic (e.g., for drain line connector 58) or PVC(e.g., for water line connector water line connector 68). Any of thebags or containers may be made of PVC. The materials for any of theabove components may be changed over time.

Fail Safe Connection of Concentrate Connectors and Water PurifierConnectors

Referring now to FIGS. 3A to 3D, example embodiments for first cassetteconcentrate connector 80 a, first container concentrate connector 80 b,second cassette concentrate connector 82 a and second containerconcentrate connector 82 b are illustrated. In general, the innerworkings of the connectors are sized differently, so that (i) firstcassette concentrate connector 80 a cannot be connected to secondcontainer concentrate connector 82 b, and (ii) second cassetteconcentrate connector 82 a cannot be connected to first containerconcentrate connector 80 b. And because (i) first cassette concentrateconnector 80 a and second cassette concentrate connector 82 a arepermanently attached to cassette 42 via their respective lines 76, 78,and (ii) first container concentrate connector 80 b and second containerconcentrate connector 82 b are permanently attached to their respectiveconcentrate container 84 a, 84 b via their respective lines 86, 88,patient P cannot connect concentrate containers 84 a, 84 b to cassette42 improperly.

FIGS. 3A to 3D in general illustrate that glucose connectors 80 a/80 bare larger in multiple respects than buffer connectors 82 a/82 b. In analternative embodiment, the buffer connectors are larger in multiplerespects than the glucose connectors. In either case, FIG. 3Aillustrates that male luer port 80 c of male luer connector 80 b has alarger outer diameter than male luer port 82 c of male luer connector 82b FIG. 3A also illustrates that female threads 80 d of male luerconnector 80 b have a larger inner diameter than the inner diameter offemale threads 82 d of male luer connector 82 b. FIGS. 3A to 3D furtherillustrate that outer annular wall 80 e of male luer connector 80 b hasa larger inner diameter than the inner diameter of outer annular wall 82e of male luer connector 82 b, while outer annular wall 80 f of femaleluer connector 80 a has a larger inner diameter than the inner diameterof outer annular wall 82 f of female luer connector 82 a.

FIG. 3B further illustrates that male threads 80 g of female luerconnector 80 a are larger in outer diameter than the outer diameter ofmale threads 82 g of female luer connector 82 a. The cross-section ofFIG. 3D confirms everything above, including (i) female threads 80 d ofmale luer connector 80 b having a larger inner diameter than the innerdiameter of female threads 82 d of male luer connector 82 b, and (ii)male threads 80 g of female luer connector 80 a having a larger outerdiameter than the outer diameter of male threads 82 g of female luerconnector 82 a. FIG. 3D also illustrates that the shroud differential“D” provided by outer annular wall 82 e of male luer connector 82 b islonger than shroud differential “d” provided by outer annular wall 80 eof male luer connector 80 b. The differently sized threads and thedifferent shroud differentials D and d, in particular, prevent patient Pfrom connecting the concentrate containers 84 a, 84 b to cassette 42improperly.

It should be appreciated that differently sized mating connectors, suchas differently sized luer mating connectors 80 a/80 b versus 82 a/82 b,may also be used for other connector pairs, including water lineconnector 68/water outlet connector 128 and drain line connector58/drain connector 118 at the connection to water purifier 110. Here,the differently sized connector pairs prevent patient P or other userfrom connecting (i) upstream water line segment 64 a to drain connector118 and/or (ii) drain line 56 to water outlet connector 128.

In one preferred embodiment, drain line connector 58 and water lineconnector 68 are threaded but are not true luer connectors, so theycannot mate with any of differently sized luer mating connectors 80 a/80b and 82 a/82 b. Connectors 58 and 68 also cannot mate with transfer set54, so the connectors may only be connected to water purifier 110. In anembodiment, drain line connector 58 and water line connector 68 areconfigured to be connected together, so that after treatment, patient Por other user may remove disposable set 40 from cycler 20 and waterpurifier 110 and connect upstream water line segment 64 a and drain line56 together via the connection of water line connector 68 to drain lineconnector 58. By doing so, WFPD in upstream water line segment 64 a andeffluent dialysis fluid in drain line 56 cannot spill from those linesupon disconnection after treatment. Configuring drain line connector 58and water line connector 68 to be connected together also preventspatient P or other user from (i) connecting drain line connector 58 towater outlet connector 128 because they are the same (male or female)connector and (ii) connecting water line connector 68 to drain connector118 because they are also the same (female or male) connector.

Different concentrate connectors 80 a/80 b and 82 a/82 b and/orconfiguring drain line connector 58 and water line connector 68 to beconnected together may, including any alternative embodiments describedin connection with FIGS. 3A to 3D, be used for any of the differentperitoneal dialysis systems 10 a to 10 d having point of use dialysisfluid preparation described herein.

Heater/Mixing Bag Connector

Referring now to FIGS. 4A to 4G in light of FIG. 1, the placement ofheater/mixing bag 62 for operation is illustrated in detail. FIG. 4Aillustrates a heating/mixing portion of housing 24 of cycler 20. Housing24 includes a heater/mixing tray 90 located at the top of housing 24 forreceiving heater/mixing bag 62. The heater of cycler 20, under controlof control unit 22, is located beneath heater/mixing tray 90 and in oneembodiment includes heating elements that contact heater/mixing tray 90.Heater/mixing tray 90 includes plural sidewalls including sidewall 92that defines a slot 94 for receiving a heater/mixing bag connector 100described in detail below. Housing 24 also defines a lid 96 connectedhingedly to the back of housing 24 at the top of heater heater/mixingtray 90. Lid 96 may be hinged open to locate and remove heater/mixingbag 62 and hinged closed onto housing 24 for insulation during heating.Lid 96 includes a sidewall 98 that mates with sidewall 92 as describedin more detail below. Lid 96 and sidewall 92 of housing 24 may be madeof metal or plastic, while heater/mixing tray 90 is made of metal, suchas aluminum, for conducting and withstanding heat.

FIG. 4B illustrates the pertinent section of sidewall 92 including slot94 in more detail. A sectioned semi-circular flange 92 a extends fromsidewall 92. Semi-circular flange 92 a may be formed with or welded tosidewall 92. Semi-circular flange 92 a helps to align heater/mixing bagconnector 100, so that the port extends horizontally through sidewall 92and roughly parallel with the bottom of heater/mixing tray 90. Slot 94in the illustrated embodiment includes an introductory V-shaped section94 a, which extends to a resting circular section 94 b. A pinch point 94c separating V-shaped section 94 a and circular section 94 b is smallerthan the contacting diameter of heater/mixing bag connector 100 in oneembodiment. Patient P or other user accordingly feels a tactile “snap”when installing heater/mixing bag connector 100 into resting circularsection 94 b, indicating a proper and final installation. Pinch point 94c also tends to hold heater/mixing bag connector 100 in place,preventing the port from translating upwardly within slot 94, e.g.,while heater/mixing bag 62 is being filled.

FIG. 4C illustrates one embodiment for heater/mixing bag connector 100.Heater/mixing bag connector 100 may be made of a material having asufficiently low physiological impact on the patient fluid and therebyon patient P. Heater/mixing bag connector 100 may be molded as a singlepiece or as multiple pieces fitted sealingly together. Heater/mixing bagconnector 100 includes a tube connection port 102 a for sealinglyattaching to heater/mixing line 60 (FIG. 1). Tube connection port 102 aextends to an outer flange 104. Outer flange 104 is offset from an innerflange 106 via an anti-rotation key 108. A bag introduction port 102 bextends from inner flange 106 into heater/mixing bag 62. In anembodiment, heater/mixing bag 62 is sealed to bag introduction port 102b via heat sealing, sonic welding or solvent bonding.

The interior lumen of bag introduction port 102 b may have a constantdiameter cylindrical shape or be nozzled. If nozzled, the axis orcenterline of the nozzle may point horizontally or point downwardlytowards the bottom of heater/mixing tray 90. The concentrates, such asglucose and buffer, are generally heavier than the WFPD with which theconcentrates are mixed. It may accordingly be desirable to point thedirection of concentrates and water entering heater/mixing bag 62downwardly, so that the concentrates and water have more time to mixbefore the lighter water separates upwardly from the heavierconcentrates.

In an embodiment, there is no tube extending off of the distal end ofintroduction port 102 b, so that concentrates and water exitintroduction port 102 b freely into heater/mixing bag 62. In analternative embodiment, a diffusing manifold (not illustrated) may beattached sealingly to the distal end of introduction port 102 b. Thediffusing manifold may, for example, be a rigid or flexible tube that iscapped at its distal end. The tube includes multiple openings orapertures spaced along its length, which allow the concentrates andwater to exit into heater/mixing bag 62. The diffusing manifold in thisway distributes the concentrates more evenly across the entire length ofheater/mixing bag 62 and forces the concentrates and the WFPD to mix asthey exit the openings or apertures spaced along the length of thediffusing manifold.

FIGS. 4D and 4E illustrate heater/mixing bag connector 100 inserted intoslot 94 of sidewall 92. FIG. 4D shows heater/mixing bag connector 100from the outside of heater pan 90, highlighting outer flange 104, whileFIG. 4E shows heater/mixing bag connector 100 from the inside of heaterpan 90, highlighting inner flange 106. In FIG. 4D, a bottom 104 a (FIG.4C) of outer flange 104 of heater/mixing bag connector 100 is bottomedout against semi-circular flange 92 a extending from sidewall 92. FIGS.4D and 4E show that outer flange 104 and inner flange 106 ofheater/mixing bag connector 100 are abutted against outer and innersurfaces, respectively, of sidewall 92. Anti-rotation key 108 resideswithin slot 94 as illustrated in more detail below. Introduction port102 b of heater/mixing bag connector 100 is illustrated as being sealedto a section of heater/mixing bag 62. Tube connection port 102 a ofheater/mixing bag connector 100 is not viewable in FIG. 4D because it iscovered by and sealed to heater/mixing line 60.

Outer flange 104 and inner flange 106 prevent heater/mixing bagconnector 100 from being rotated about an axis perpendicular to thecentral axis A (FIG. 4E) through tube connection port 102 a whenheater/mixing bag 62 is being filled with concentrates and WFPD forheating and mixing. As discussed above, the concentrates are heavierthan the WFPD. Thus, if heater/mixing bag connector 100 is rotated suchthat the distal end of introduction port 102 b is pointed up towards thetop of heater/mixing bag 62 during filling, the lighter water can flowover the heavier and falling concentrate, tending to prevent propermixing. Outer flange 104 and inner flange 106 prevent such rotating andtilting from occurring, helping to ensure that the concentrates and WFPDare injected straight across the inside of heater/mixing bag 62, towardsthe far side of the bag 62.

In FIG. 4F, outer flange 104 shown in FIG. 4D has been removed so thatanti-rotation key 108 may be seen in full. FIG. 4F illustrates aninternal section of heater/mixing bag connector 100 to highlightanti-rotation key 108, which resides within V-shaped section 94 a ofslot 94 when heater/mixing bag 62 is loaded into heater/mixing tray 90.As illustrated, anti-rotation key 108 includes an upper horizontalmember 108 a and a vertical, centrally located member 108 b, forming a“T” shape. Upper horizontal member 108 a extends to each edge ofV-shaped section 94 a, preventing the rotation of heater/mixing bagconnector 100 in either a clockwise or counterclockwise direction aboutthe central axis A (FIG. 4F) through tube connection port 102 a.Centrally located vertical member 108 b adds rigidity to heater/mixingbag connector 100. Anti-rotation key 108 serves the additional purposeof preventing heater/mixing bag 62 from being loaded upside down intoheater/mixing tray 90. If patient P or another user attempts to loadheater/mixing bag 62 upside down into heater/mixing tray 90, upperhorizontal member 108 a becomes wedged within V-shaped section 94 a ofslot 94, so that tube connection port 102 a cannot snap-fit intocircular section 94 b of slot 94. Patient P or other user senses theimproper fit and reloads heater/mixing bag 62 in the proper orientationwithin heater/mixing tray 90.

FIG. 4G illustrates that once patient P or other user loadsheater/mixing bag 62 properly into heater/mixing tray 90, patient P orother user closes (e.g., hingedly closes) lid 96, such that sidewall 98of lid 96 meets sidewall 92 of heater/mixing tray 90. In the illustratedembodiment, lid 96 is sized and positioned such that when lid is closed,the bottom edge 98 a of sidewall 98 closes onto outer flange 104 ofheater/mixing bag connector 100. This closure, along with thesnap-fitting of tube connection port 102 a into circular section 94 b ofslot 94 prevents the upward vertical translation or displacement ofheater/mixing bag connector 100 within slot 94, e.g., due to the fillingof heater/mixing bag 62 with concentrates and WFPD.

In an alternative embodiment (not illustrated), the heater/mixing bagconnector is configured such that patient P or other user loads the portinto slot 94 as before. Patient P or the other user then rotates theport, e.g., 45° clockwise, until a handle provided by the port isapproximately horizontal, which in turn orients internal diameter ribsof the alternative connector residing within circular section 94 b ofslot 94, such that the ribs abut the wall of resting circular section 94b to resist vertical displacement of the alternative port within slot 94during the filling of heater/mixing bag 62.

Heater/mixing bag connector 100 or the alternative heater/mixing bagconnector just described, including any alternative embodimentsdescribed in connection with FIGS. 4A to 4G, may be used for any of thedifferent dialysis systems 10 a to 10 d having point of use dialysisfluid preparation described herein.

Mixing Regime, Dialysis Fluid Testing, and Treatment

Referring now to FIG. 5, one embodiment for mixing dialysis fluid at thepoint of use using multiple concentrates and WFPD is illustrated bymethod 210. At oval 212, method 210 begins. At block 214, patient P orother user performs setup for system 10 as discussed above, including(i) turning cycler 20 on, (ii) placing heater/mixing bag 62 onto cycler20, (iii) connecting upstream water line segment 64 a to water purifier110, (iv) connecting drain line 56 to water purifier 110, (v) connectingfirst cassette concentrate connector 80 a to first container concentrateconnector 80 b, and (vi) and connecting second cassette concentrateconnector 82 a to second container concentrate connector 82 b.

At block 216, cycler 20 performs dry integrity tests which pressurecheck cassette 42, water accumulator 66 and heater/mixing bag 62, forexample. At block 222, after determining that disposable set 40 passesthe integrity tests, control unit 22 may turn water purifier 110 onautomatically, sync wirelessly with its control unit 112, and tellcontrol unit to prepare WFPD, e.g., specifying volume and temperature.To prepare WFPD, in one embodiment viewing FIG. 1, control unit 112 ofwater purifier 110 causes the water purifier to pump purified water at adesired pressure set by pressure regulator 130, at a desiredtemperature, e.g., at 20° C. to 30° C., through sterile sterilizinggrade filters 70 a and 70 b, and through upstream water line segment 64a into water accumulator 66 via water inlet 66 a. Pressure regulator 130may set the water outlet pressure to on the order of 137.9 to 275.8 kPa(20 to 40 psig) to force purified water through sterile sterilizinggrade filters 70 a and 70 b to produce WFPD residing within wateraccumulator 66. Water purifier 110 may for example pump 2 to 3 liters ofpurified water at 20° C. to 30° C. through sterile sterilizing gradefilters 70 a and 70 b to water accumulator 66. Up until block 216,cycler 20 is not needed for fluid control, other than to close the fluidvalve chamber 46 at cassette 42 to downstream water line segment 64 band/or close occluder 26 at patient line 50 and drain line 56, becausewater accumulator 66 decouples or isolates water purifier 110 fromdisposable set 40 in terms of fluid pressure and flowrate. It should beappreciated, however, that control unit 22 of cycler 20 may initiate thepreparation of WFPD by sending a command wired or wirelessly to controlunit 112 of water purifier 110 to prepare a desired quantity of WFPD ata certain temperature. The elevated temperature of WFPD lowers theheating burden on cycler 20.

At block 224, control unit 22 causes cycler 20 to perform a cassette 42prime sequence. To prime cassette 42, control unit 22 causes cycler 20to open fluid valves 46 at cassette 42 to (i) first concentratecontainer line 86 and (ii) drain line 56, allowing pump chambers 44 toprime (e.g., alternatingly to achieve somewhat continuous flow) firstconcentrate line 76/86 with first concentrate from first concentratecontainer 84 a, pushing air in those lines to drain 116. Control unit 22then causes cycler 20 to (i) close cassette fluid valve 46 to firstconcentrate line 76/86, (ii) maintain cassette fluid valve 46 to drainline 56 open, and (iii) open fluid valve 46 at cassette 42 to secondconcentrate line 78/88, allowing pump chambers 44 to prime (e.g.,alternatingly to achieve somewhat continuous flow) second concentrateline 78/88 with second concentrate from second concentrate container 84b, pushing air from those lines to drain 116. Control unit 22 thencauses cycler 20 to (i) close cassette fluid valve 46 to secondconcentrate line 78/88, (ii) maintain cassette fluid valve 46 to drainline 56 open, and (iii) open the fluid valve chamber 46 to downstreamwater line segment 64 b, allowing fluid pump chambers 44 to prime (e.g.,alternatingly to achieve somewhat continuous flow) line segment 64 b anddrain line 56 with WFPD from water accumulator 66, pushing air fromthose lines to drain 116.

Initially, drain line 56 will be filled with a combination of WFPD andconcentrates due to the priming of concentrate lines 76/86 and 78/88with concentrate. At priming block 224, or at some other step prior totesting the mixed dialysis fluid, control unit 22 causes cycler 20 topump enough WFPD from water accumulator 66 so that drain line is primedcompletely with WFPD, and so that WFPD is flowed to a conductivitysensor 132. When WFPD is at conductivity sensor 132, control unit 112 ofwater purifier 110 may take one or more conductivity reading fromconductivity sensor 132 for the WFPD and either (i) compare thereading(s) with an expected reading for WFPD and send, wired orwirelessly, a “conductivity sensor reading good” or “conductivity sensorreading fails” output to control unit 22 of cycler 20, which takesappropriate action, or (ii) sends the conductivity reading(s) wired orwirelessly to control unit 22 of cycler 20, so that control unit 22 maydetermine, e.g., compare the reading to a look-up table, if theconductivity sensor reading is good or not and take appropriate action.The above calibration procedure may be performed using any one or morefluid having a known conductivity.

At block 226 mixing begins, wherein control unit 22 causes cycler 20 to(i) close the fluid valve 46 of cassette 42 leading to drain line 56,(ii) open the fluid valve 46 of cassette 42 leading to downstream waterline segment 64 b and (iii) open the fluid valve 46 of cassette 42leading to heater/mixing bag 62, allowing fluid pump chambers 44 to pump(e.g., alternatingly to achieve somewhat continuous flow) a desiredamount of WFPD from water accumulator 66, through downstream water linesegment 64 b, through cassette 42, through heater/mixing line 60 andinto heater/mixing bag 62 via heater/mixing bag connector 100. In oneembodiment, the initial desired amount of WFPD is a percentage of atotal desired amount of WFPD, which is based on the prescribed patientfill volume plus an additional volume, e.g., 300 to 500 milliliters overthe prescribed fill volume. One suitable percentage is ten percent.

At block 228, control unit 22 causes cycler 20 to (i) close the fluidvalve chamber 46 at cassette 42 to downstream water line segment 64 b,(ii) maintain open the fluid valve chamber 46 at cassette 42 toheater/mixing bag 62, and (iii) open the fluid valve chamber 46 atcassette 42 to first, e.g., glucose, concentrate line 76/86, allowingfluid pump chambers 44 to pump (e.g., alternatingly to achieve somewhatcontinuous flow) a desired amount of first concentrate, e.g., glucose,from first concentrate container 84 a, through first concentrate line76/86, through cassette 42, through heater/mixing line 60 and intoheater/mixing bag 62 via heater/mixing bag connector 100. In oneembodiment, the desired amount of first concentrate, e.g., glucose, is atotal desired amount of first concentrate, which is based on theprescribed patient fill volume (plus an extra 300 to 500 milliliters ofmargin) and the prescribed dialysis fluid chemistry. Example approveddialysis fluid chemistries include (i) 1.5% dextrose monohydrate (orglucose monohydrate)=1.36% anhydrous dextrose (or anhydrous glucose),(ii) 2.5% dextrose monohydrate (or glucose monohydrate)=2.27% anhydrousdextrose (or anhydrous glucose), and (iii) 4.25% dextrose monohydrate(or glucose monohydrate)=3.86% anhydrous dextrose (or anhydrousglucose).

At block 230, control unit 22 causes cycler 20 to (i) close the fluidvalve chamber 46 at cassette 42 to first concentrate line 76/86, (ii)maintain open the fluid valve chamber 46 at cassette 42 to heater/mixingbag 62, and (iii) open the fluid valve chamber 46 at cassette 42 tosecond, e.g., buffer, concentrate line 78/88, allowing fluid pumpchambers 44 to pump (e.g., alternatingly to achieve somewhat continuousflow) a desired amount of second concentrate, e.g., buffer, from secondconcentrate container 84 b, through second concentrate line 78/88,through cassette 42, through heater/mixing line 60 and intoheater/mixing bag 62 via heater/mixing bag connector 100. In oneembodiment, the desired amount of second concentrate, e.g., buffer, is atotal desired amount of second concentrate, which is again based on theprescribed patient fill volume (plus an extra 300 to 500 milliliters ofmargin) and the prescribed dialysis fluid chemistry.

At block 232, control unit 22 causes cycler 20 to (i) close the fluidvalve chamber 46 at cassette 42 to second concentrate line 78, (ii)maintain open the fluid valve chamber 46 at cassette 42 to heater/mixingbag 62, and (iii) open the fluid valve chamber 46 at cassette 42 todownstream water line segment 64 b, allowing fluid pump chambers 44 topump (e.g., alternatingly to achieve somewhat continuous flow) theremaining amount, e.g., ninety percent, of WFPD from water accumulator66, through downstream water line segment 64 b, through cassette 42,through heater/mixing line 60 and into heater/mixing bag 62 viaheater/mixing bag connector 100. At this point the correct amounts ofWFPD, first concentrate, e.g., glucose, second concentrate, e.g.,buffer, and . . . nth concentrate (method 210 is scalable for anydesired number of concentrates, including only a single concentrate) toprepare the prescribed amount of the prescribed peritoneal dialysissolution. The prescribed amount will reside within heater/mixing bag 62and cassette 42. That is, in one embodiment pumping the remainingpercentage of WFPD ends when the final pump stroke of water reaches oneof the fluid pump chambers 44.

At block 234, control unit 22 causes cycler 20 to (i) turn on the fluidheater within housing 24 to heat the WFPD and concentrates withinheater/mixing bag 62 (although heating may begin earlier as long asthere is some type of fluid within heater/mixing bag 62) and (ii)perform a “waffling” sequence. To perform the waffling sequence, controlunit 22 in an embodiment causes cycler 20 to close all fluid valvechambers 46 at cassette 42 except for the fluid valve chamber 46 toheater/mixing line 60 and heater/mixing bag 62. Fluid pump chambers 44are stroked sequentially and repeatedly to (i) pull WFPD andconcentrates from heater/mixing bag 62 into the pump chambers and (ii)push WFPD and concentrates from the pump chambers to heater/mixing bag62. Control unit 22 may be programmed to stroke fluid pump chambers 44together so that they both pull and push at the same time, oralternatingly so that one pump chamber 44 pulls from heater/mixing bag62, while the other pump chamber 44 pushes to heater/mixing bag 62,creating turbulence in heater/mixing line 60.

In an alternative waffling embodiments, control unit 22 is programmed tocause the first and second pump chambers 44 to pump to each other one ormore time before pushing fluid back to heater/mixing bag 62.Additionally, to further create turbulence, it is contemplated in any ofthe waffling embodiments to program control unit 22 to cause theelectrical input signal to one or more variable orifice pneumatic valvefor pump chambers 44 to vary during the waffling sequence, e.g., in apulse, cyclic or sinewave like manner, such as 3.5 kPa (0.5 psig) up anddown from a mean pumping pressure, such as 24.8 kPa (3.6 psig).Moreover, for any of the waffling embodiments, it is contemplated topump from and to heater/mixing bag 62 until, for example, 200 percent ofthe heater/mixing bag volume is pumped back and forth. The 200 percentor other desired percentage may be achieved within the time needed toproperly heat the mixed dialysis fluid to, e.g., 35° C. to 37° C.

At diamond 236 after waffling, and remembering that drain line 56 isprimed with WFPD, control unit 22 causes cycler 20 to close all fluidvalve chambers 46 at cassette 42 except for the fluid valve chamber 46to drain line 56, allowing fluid pump chambers 44 to pump (e.g.,alternatingly to achieve somewhat continuous flow) a desired sampleamount, e.g., 80 to 100 milliliters, of fresh mixed dialysis fluid downdrain line 56 to conductivity sensor 132 to take one or moreconductivity reading of the of fresh, mixed dialysis fluid. In anembodiment, control unit 22 is programmed to cause cycler 20 to thenpump WFPD down drain line 56 to conductivity sensor 132 after the, e.g.,80 to 100 milliliters, slug of mixed dialysis solution to provide aclear conductivity sensing differentiation both before and after theslug. To provide the after-slug WFPD, control unit 22 is programmed inone embodiment to (i) close the cassette fluid valve 46 leading toheater/mixing line 60, open the cassette fluid valve 46 leading todownstream water line segment 64 b and water accumulator 66, open thecassette fluid valve 46 leading to drain line 56, allowing fluid pumpchambers 44 to pump (e.g., alternatingly to achieve somewhat continuousflow) a desired amount of WFPD from water accumulator 66, throughdownstream water line segment 64 b, through cassette 42, down drain line56 to conductivity sensor 132.

Different PD dialysis fluids are typically differentiated by dextrose orglucose levels. For example, there is a 4.25% dextrose monohydrate (orglucose monohydrate)=3.86% anhydrous dextrose (or anhydrous glucose) PDdialysis fluid. 4.25% dextrose may, depending on its chemicalformulation, have a corresponding and repeatable conductivitymeasurement of 11.64 mS/cm. The other two common dialysis fluid types(1.5% dextrose and 2.5% dextrose) produce different corresponding andrepeatable conductivity measurements. Control unit 22 can thereforeverify if the dialysis fluid has been mixed properly by comparing itsmeasured conductivity to an expected conductivity stored in a look-uptable.

As part of block 234, and as described similarly at block 224, whenconductivity sensor 132 reads the slug of freshly mixed dialysis fluid,control unit 112 of water purifier 110 takes one or more conductivityreading from conductivity sensor 132 for the mixed dialysis fluid slugand either (i) compares the reading(s) with an expected reading for WFPDand sends, wired or wirelessly, a “mixed dialysis fluid reading good” or“mixed dialysis fluid reading failed” output to control unit 22 ofcycler 20 which takes appropriate action, or (ii) sends the conductivityreading(s) wired or wirelessly to control unit 22 of cycler 20, so thatcontrol unit 22 may determine, e.g., compare the reading to a look-uptable, if the mixed dialysis fluid reading(s) is good or not. Thecomparison may be to a range, e.g., within five percent of the setpointconductivity.

If the result at diamond 236 is that the measured dialysis fluid isoutside the range of the setpoint conductivity, method 210 at diamond238 inquires whether an additional amount of waffling has already beenperformed. If an additional amount of waffling has already beenperformed as determined at diamond 238, control unit 22 of cycler 20 atblock 240 causes the current batch of mixed dialysis fluid to be sent todrain 116 and performs the mixing process again, starting at block 226.If an additional amount of waffling has not yet been performed asdetermined at diamond 238, control unit 22 of cycler 20 at block 242causes an additional amount of waffling to occur, wherein another 50percent of the heater/mixing bag volume, for example, is pumped back andforth, after which method 210 returns to diamond 236 to test theadditionally waffled dialysis fluid again. In one embodiment, precedingthe additional waffling at block 238, control unit 22 may cause a secondsample of mixed dialysis fluid to be sent to conductivity sensor 132 forre-measurement (in case of an erroneous measurement in the first sample,e.g., due to air).

It should be appreciated that when conductivity sensor 132 is not usedfor sampling, the sensor may be bypassed so it is not used at all or beused for a different purpose, e.g. in water purifier 110 to sample theconductivity of water being purified. FIG. 16 illustrates variousembodiments for providing this functionality. FIG. 16 illustratesconductivity sensor surrounded by six valves 286 a to 286 e, which maybe electrically actuated solenoid valves (e.g., normally closed,energized open) under the control of control unit 112. In a normaldraining operation, when mixed fluid sample testing is not desired,control unit 112 causes valves 286 b, 286 c, 286 d and 286 e provided inparallel flow paths or lines 292 a and 292 b to be closed and valve 286f to be open, so that used dialysis fluid, WFPD, unused concentrate orcombinations thereof may flow through drain line 56, valve 286 f, todrain 116 at water purifier 110. Here, conductivity sensor 132 isbypassed completely and valve 286 a may be opened or closed to allow ornot allow purified water to flow out water line 64 as desired.Alternatively during a draining operation, when mixed fluid sampletesting is not desired, control unit 112 causes (i) valves 286 d and 286e to be closed and valve 286 f to be open so that used dialysis fluid,WFPD, unused concentrate or combinations thereof may flow through drainline 56, valve 286 f, to drain 116 at water purifier 110 and (ii) valve286 a to be closed and valves 286 b and 286 c to be open so thatpurified water flows past conductivity sensor 132 for sensing. It shouldbe appreciated that control unit 112 may control valve 286 a to beclosed and valves 286 b and 286 c to be open to test the purified wateroutput regardless of whether or not effluent is flowing through drainline 56 to drain 116. When mixed fluid sampling is desired, control unit112 causes valves 286 b, 286 c and 286 f to be closed and valves 286 dand 286 e to be open so that the mixed fluid sample flows pastconductivity sensor 132 to drain. Here, valve 286 a may be open orclosed to allow or not allow purified water to flow through main waterline 292 c.

In an alternative embodiment, valve 286 a is not provided andconductivity sensor 132 is moved to where valve 286 a is located in FIG.16, so that conductivity sensor 132 may replace downstream conductivitysensor 170 b. Valves 286 b and 286 c are moved outside of theconnections of parallel lines 292 a and 292 b to main water line 292 c,so that control unit 112 can selectively allow conductivity sensor 132to sense purified water flowing through main water line 292 c. Whenvalves 286 b and 286 c are closed, control unit 112 may close valve 286f and open valves 286 d and 286 e, so that sample mixed fluid may flowpast conductivity sensor 132 to drain. In this alternative embodiment,sample mixed fluid may not flow past conductivity sensor 132 to drainwhen purified water is flowing through main water line 292 c. Also, allpurified water flowing through main water line 292 c sees conductivitysensor 132, so that selective sampling of purified water flowing throughmain water line 292 c is not possible.

Returning to method 210, if the result at diamond 236 is that themeasured dialysis fluid is within the range of the setpointconductivity, method 210 proceeds with treatment. Here, at diamond 244,control unit 22 of cycler 20 determines if the upcoming fill procedurefor patient P is a first fill procedure for the current treatment. Ifso, at block 246, control unit 22 causes cycler 20 to open the fluidvalve 46 of cassette 42 to patient line 50 and prime patient line 50 upto patient connector 52 with properly mixed dialysis fluid. Patientconnector 52 may for example be fitted with a tip protector having ahydrophobic membrane that allows air to be pushed through the membraneby the properly mixed dialysis fluid filling patient line 50. Oncepatient line 50 is primed, user interface 30 prompts patient P toconnect patient connector 52 to the patient P's transfer set 54, leadingto patient P's indwelling catheter.

At diamond 248, control unit 22 determines if patient P is already fullwith used dialysis fluid. Control unit 22 and user interface 30 ofcycler 20 may, for example, query patient P during treatment setupwhether or not an initial drain is needed. If so, or if the upcomingfill procedure is not the first fill procedure as determined at diamond244 (meaning patient P already has a fill volume plus an amount ofultrafiltration removed), method 210 performs a drain procedure forpatient P at block 250. At block 250, control unit 22 causes cycler 20to (i) maintain fluid valve 46 of cassette 42 to patient line 50 openand (ii) open the fluid valve 46 of cassette 42 to drain line 56,allowing fluid pump chambers 44 to pump (e.g., alternatingly to achievesomewhat continuous flow) used dialysis from the patient's peritoneum todrain 116 (either full drain for continuous cycling peritoneal dialysis(“CCPD”) or a partial drain for a tidal PD treatment, whichever isprescribed), recording the drained amount for purposes of determiningultrafiltration removed over the previous twenty-four hours (assumingconsecutive treatments start at the same time of the night).

At diamond 248, if patient P does not have used dialysis fluid toinitially drain, or when the drain at block 250 is completed, method 210performs a fill procedure for patient P at block 252. At block 252,control unit 22 causes cycler 20 to (i) maintain fluid valve 46 ofcassette 42 to patient line 50 open and (ii) open the fluid valve 46 ofcassette 42 to heater/mixing line 60, allowing fluid pump chambers 44 topump (e.g., alternatingly to achieve somewhat continuous flow) properlymixed fresh dialysis fluid from heater/mixing bag 62 to patient P. Theamount of properly mixed fresh dialysis fluid pumped is prescribed by adoctor or clinician. As discussed above, control unit 22 is programmedin one embodiment to prepare a greater amount of fresh dialysis fluidfor storage in heater/mixing bag 62 than is delivered to patient Pduring the fill procedure, e.g., 2.5 liters when only 2 liters is pumpedto the patient. There is accordingly likely to be some amount of freshdialysis fluid, e.g., 500 milliliters, residing within heater/mixing bag62 after the fill procedure.

At block 254, method 210 preforms a patient dwell procedure. During thedwell procedure, control unit 22 causes cycler 20 to close the fluidvalve 46 of cassette 42 to patient line 50. The therapeutic effect ofthe newly mixed fresh dialysis fluid takes place during the dwell phase.Waste and toxins move osmotically from the blood of patient P, throughpatient P's peritoneal membrane, into the dialysis fluid. Excess fluidfrom patient P is also removed into the dialysis fluid asultrafiltration (“UF”), typically seven percent of the fill volume, soroughly 140 milliliters for a 2 liter fill volume). The dwell period atblock 254 may last one to two hours, for example.

At diamond 256, control unit 22 determines whether there is anotherpoint of use preparation cycle for the current treatment. If so, atblock 258, control unit 22 causes cycler 20, during the dwell period, toinstruct water purifier 110 to prepare another batch, e.g., 2 to 3liters, of WFPD and deliver the batch at a desired temperature to wateraccumulator 66. Preparing WFPD at block 258 may be done according thevalving procedure described in connection with block 222. Also, becausewater accumulator 66 decouples cycler 20 from water purifier 110 interms of fluid flow and pressure, the procedure of block 258 does nothave to wait until the dwell period and may in alternative embodimentsbegin during the patient fill procedure at block 252 or even at thepatient drain procedure at block 250, providing additional time toprepare the next batch of dialysis fluid, which occurs during the dwellprocedure, starting at block 226 and running through the mixing steps toblock 234.

It should also be appreciated that control unit 22 knows how much WFPDresides in water accumulator 66 at any given time because it knows howmuch it told water purifier 110 to send to accumulator 66 and how muchit caused cycler 20 to pump from accumulator 66. To not overfill wateraccumulator 66, control unit 22 is accordingly programmed to calculatehow much additional WFPD is needed at block 258, which in combinationwith any residual WFPD residing in water accumulator 66 sums to adesired overall amount of WFPD in the accumulator.

Similarly, as discussed above, there is likely to be residual freshdialysis fluid in heater/mixing bag 62 when the second, third, fourth,etc., batch of dialysis fluid is made at mixing steps 226 to 234.Control unit 22 knows how much dialysis fluid was delivered toheater/mixing bag 62 in the previous mixing and heating procedure andhow much of that dialysis fluid was delivered to patient P at theprevious fill procedure at block 252. Control unit 22 therefore knowshow much residual properly mixed dialysis fluid remains in heater/mixingbag 62 and calculates how much new dialysis fluid to mix with theresidual fluid to achieve the same desired extra amount, e.g., 300 to500 milliliters. So for example, if 2.5 liters of fresh dialysis fluidwere prepared initially in heater/mixing bag 62 and 2 liters weredelivered to patient P in the previous fill, control unit 22 the nexttime around prepares only 2 liters of new dialysis fluid to reach thesame desired 2.5 liters (including desired 500 milliliter margin) inheater/mixing bag 62 prior to the next patient fill procedure.

It is contemplated that a doctor or clinician may prescribe differentdextrose or glucose levels for different patient fill procedures of thesame treatment. For example, a first fill may be prescribed to use 1.5%dextrose monohydrate dialysis fluid, while a second fill uses 2.5%dextrose monohydrate dialysis fluid, and a third fill uses 4.25%dextrose monohydrate dialysis fluid. When this is done, and when thereis a residual volume of dialysis fluid within heater/mixing bag 62 at adextrose level different from what is prescribed for the current batchof dialysis fluid, control unit 22 may be programmed to cause cycler 20perform any one of the following: (i) pump the residual dialysis fluidto drain 116 and prepare a new batch of dialysis fluid plus any desiredsurplus at the prescribed dextrose or glucose level, (ii) keep theresidual dialysis fluid and prepare a new batch of dialysis fluid in anamount to maintain the desired surplus and at the prescribed dextrose orglucose level, knowing that the resulting mixture will be different thanthe prescribed dextrose or glucose level due to the residual dialysisfluid having the different dextrose or glucose level, or (iii) keep theresidual dialysis fluid and prepare a new batch of dialysis fluid in anamount to maintain the desired surplus and at a dextrose or glucoselevel that in combination with the residual dialysis fluid having thedifferent dextrose or glucose level will meet the prescribed dextrose orglucose level. Option (ii) is acceptable because the resulting dextroseor glucose level will be in a physiologically safe range for patient P,e.g., at or between the regulatorily accepted 1.5% to 4.25% dextrosemonohydrate dialysis fluid levels. In an embodiment, the look-up tablewithin control unit 22 or control unit 112 is programmed to storesetpoint conductivity values for expected combinations, e.g., for asituation in (ii) where 500 milliliters of 1.5% dextrose monohydratedialysis fluid is combined with 2 liters of 2.5% dextrose monohydratedialysis fluid. Setpoint conductivity values for expected combinationsalso includes combinations that occur when a doctor or clinicianprescribes an optimized, physiologically safe dextrose or glucose levelfor patient P, e.g., at or between the regulatorily accepted 1.5% to4.25% dextrose monohydrate dialysis fluid levels.

If there is no additional point of use preparation cycle for the currenttreatment as determined at diamond 256, control unit at diamond 260determines if patient P's treatment prescription calls for a last bagfill for patient P. The last bag is connected to connector 74 for thelast bag or sample line 72 in one embodiment. The last bag typicallyincludes a premixed and sterilized dialysis fluid having a higherdextrose or glucose level and a chemical formulation that cannot beprepared using the first and second concentrates in first and secondconcentrate containers 84 a and 84 b.

If there is a last bag fill for patient P, as determined at diamond 260,control unit 22 at block 262 causes cycler 20 to perform a patientdrain, e.g., according to the drain valving sequence discussed at block250. Control unit 22 at block 264 then causes cycler 20 to perform apatient fill using last bag dialysis fluid from the last bag connectedto connector 74 and the fill valving procedure described at block 252 inone embodiment. After the last bag fill, method 210 ends at oval 270.

If there is not a last bag fill for patient P, as determined at diamond260, control unit 22 at diamond 266 determines whether patient P'sprescription calls for patient P to end treatment dry or with the lastfill volume remaining in patient P's peritoneal cavity. That is, controlunit 22 determines whether there is a final patient drain procedure ornot. If not, treatment ends at oval 270. If so, control unit 22 at block262 causes cycler 20 to perform a patient drain, e.g., according to thedrain valving sequence discussed at block 250. After the final drain,method 210 ends at oval 270.

At the end of treatment at oval 270, control unit 22 is programmed inone embodiment to cause cycler 20 to pump as much remaining freshdialysis fluid, used dialysis fluid, WFPD and concentrates to drain 116as possible. Nevertheless, there will likely be some fluid remainingwithin disposable set 40. As described above, water line connector 68and drain line connector 58 may be connected together at the end oftreatment so that no fluid can spill out of those lines when disposableset 40 is removed from cycler 20 and water purifier 110.

In one alternative embodiment to method 210, when patient P isprescribed a relatively low fill volume, e.g., for a pediatrictreatment, control unit 22 may be programmed to cause cycler 20 toprepare multiple fill volumes worth of dialysis fluid at once and storethe multiple fill volumes plus perhaps an extra amount in heater/mixingbag 62. In such a situation, the steps of method 210 up to block 244 arethe same. Afterwards, however, control unit is programmed to causecycler 20 to perform at least one additional fill without theintermediate mixing steps set forth from block 226 to block 234.

Advantages of Water Accumulator

Water accumulator 66 provides many advantages, for example, the fluidflow and pressure decoupling of cycler 20 and water purifier 110discussed above. Besides allowing WFPD to be made while cycler 20 isperforming treatment, the pressure decoupling also protects cycler 20and cassette 42 in a situation in which one or both sterile sterilizinggrade filters 70 a and 70 b fail, which could allow the regulatedoperating pressure of water purifier 110 driving sterile sterilizinggrade filters 70 a and 70 b to be seen downstream from the filters. Ifsuch pressure, e.g., 137.9 to 275.8 kPa (20 to 40 psig), were to reachcassette 42, which cycler 20 in various embodiments operates atpressures of up to only 48.3 kPa (7 psig) positive pressure and −34.5kPa (−5 psig) suction pressure, closed cassette valves 46 would beforced open and pump chamber chambers 44 would be forced to an openend-of-stroke position. Cycler 20 would thereby become inoperable. Wateraccumulator 66 prevents this situation by providing a place to absorbthe overpressure, providing enough time for water purifier 110 to sensea corresponding pressure drop and take appropriate action, such asentering a safe mode in which its pumps are shut down and an alert issent wired or wirelessly to cycler 20, which in turn alarms audibly,visually or audio-visually at user interface 30.

Other advantages provided by water accumulator 66 include allowingsterile sterilizing grade filters 70 a and 70 b to be operated at lowerpressures and to thus be more economical. Lower operating pressureswithin water purifier 110 also produces less wear on its components.

Alternative to Water Accumulator

Referring now to FIG. 6, one embodiment of an alternative dialysissystem 10 b having point of use dialysis fluid preparation isillustrated. System 10 b has many of the same components as system 10 a,and like elements, including all alternative embodiments discussed forsuch elements, are numbered the same. For ease of illustration, only aportion of cycler 20 and water purifier 110 are illustrated. The primarydifference between systems 10 a and 10 b is that water accumulator 66 isnot provided in system 10 b. Instead, system 10 b provides arecirculation loop 200 having a disposable portion including adisposable recirculation line 202 a and a disposable recirculationconnector 202 b, and a water purifier portion including a water purifierrecirculation line 204 a and a water recirculation connector 204 b.

Recirculation loop 200 is also provided with a pump 140, which iscontrolled by control unit 112 to recirculate a certain percentage ofthe WFPD exiting sterile sterilizing grade filters 70 a and 70 b. In theillustrated example, pump 140 pulls 70 milliliters per minute from 300milliliters per minute exiting sterile sterilizing grade filters 70 aand 70 b. The resulting 230 milliliters per minute of flow to cassette42 at cycler 20 is sufficient. The pressure in disposable recirculationline 202 a and the portion of water purifier recirculation line 204 aleading from water circulation connector 204 b to the inlet of pump 140is normally low because the line begins downstream of sterilesterilizing grade filters 70 a and 70 b, which have caused a largepressure drop. If there is a breach at one or more of sterilesterilizing grade filters 70 a and 70 b, the low pressure portion ofrecirculation loop 200 absorbs the increase in downstream pressure andprovides enough time for water purifier 110 to sense a correspondingpressure drop and take appropriate action, such as entering a safe modein which its pumps are shut down and an alert is sent wired orwirelessly to cycler 20, which in turn alarms audibly, visually oraudio-visually at user interface 30.

Alternative to Drain Line Sensing

Referring now to FIG. 7, one embodiment of an alternative dialysissystem 10 c having of point of use dialysis fluid preparation isillustrated. System 10 c has many of the same components as system 10 aand like elements, including all alternative embodiments discussed forsuch elements, are numbered the same. Point of use dialysis fluidpreparation systems 10 a, 10 b and 10 d each show conductivity sensor132 located in drain line 56 at water purifier 110. System 10 c locatesconductivity sensor 132 instead inside cycler 20 and in a separatesample line 206 a, 206 b, 206 c and 206 d, not drain line 56. In theillustrated embodiment, sample line portions 206 a and 206 d are part ofdisposable set 40, while sample line portions 206 b and 206 c, placed influid communication with disposable sample line portions 206 a and 206d, respectively, are connected to conductivity sensor 132 and arepermanent within housing 24 of cycler 20.

Disposable sample line portion 206 d leads to a sample bag 208. Whenloading disposable set 40 in system 10 c, patient P or other userconnects disposable sample line portions 206 a and 206 d to appropriateconnectors located at housing 24 of cycler 20. The ends of sample lineportions 206 a and 206 d may be configured to connect together aftertreatment like water line connector 68 and drain connector 58 describedabove, so that disposable set 40 may be disposed of easily withoutspillage.

Method 210 of FIG. 5 operates the same with system 10 c except that whenchecking a mixed sample at diamond 236, control unit 22 of cycler 20causes cassette fluid valves 46 leading to (i) heater/mixing line 60 andheater/mixing bag 62 and (ii) sample line 206 a, 206 b, 206 c and 206 dto open (instead of drain line 56), allowing fluid pump chambers 44 ofcassette 42 to pump a desired sample amount of mixed dialysis fluid,e.g., 80 to 100 milliliters, from heater/mixing bag 62 to conductivitysensor 132. As before, the sample is preceded and followed by thepumping via cassette 42 of WFPD from water accumulator 66 toconductivity sensor 132. WFPD and the mixed dialysis fluid sample arecollected in sample bag 208.

Alternative Mixing Regime and Dialysis Fluid Testing

FIG. 8 illustrates a further alternative system 10 d for proportioningfluids from WFPD and at least a first concentrate in an embodiment ofthe present disclosure. System 10 d is generally intended for theon-site preparation of treatment fluids and for the treatment of thepatient with the prepared fluids. In an embodiment, system 10 d isconfigured to treat patients suffering from renal insufficiency, and inparticular using peritoneal dialysis cycler 20. System 10 d is alsoconfigured to prepare a peritoneal dialysis fluid by mixing purifiedwater (on site prepared) and concentrates and for treating a patient ina peritoneal dialysis treatment.

System 10 d as before includes a water purifier 110 and a cycler 20. Aproportioning device may be said to be made of a peritoneal dialysis(“PD”) cycler 20, which operates a circuit of disposable set 40, whichincludes a cassette 42 to which a plurality of lines and a container,such as a heater/mixing bag 62 configured to receive a treatment fluid,are connected.

In the illustrated embodiment of FIG. 8, water purifier 110 receiveswater from a house water source 150, such as a continuous source ofpottable or drinkable water from a patient's home. In variousembodiments, water purifier 110 may be installed in a room having accessto the water source 150 to provide WFPD to cycler 20 as discussedherein.

A water softener module 152 may be provided in order to reduce/controlwater hardness. Water softener module in the illustrated embodimentincludes a pre-filter 154 to remove dirt and sediment and a carbonfilter 156 to further remove contaminants and impurities. Watersoftening may alternatively or additionally be achieved using limesoftening or ion-exchange resins, as known in the art. FIG. 8schematically shows an ion-exchange resin cartridge 158 and regeneratingsalts 160, such as NaCl salts.

It should be appreciated that water softener module 152 is optional andmay not be present. It should also be appreciated that the waterpurifiers 110 of any of systems 10 a to 10 d discussed herein, andindeed with any of the alternative embodiments discussed herein, may beprovided with water softener module 152 even though the module is notillustrated or described with those systems or embodiments.

An exemplary embodiment of water purifier 110 is discussed in connectionwith FIG. 16. Softened (or unsoftened) water enters water purifier 110via a water intake 162. FIG. 16 illustrates that water purifier 110includes a purifying circuit 164 that accepts water from water intake162 and that includes a reverse osmosis module 166 to purify water fromthe intake 162. In particular, feed water enters water purifier 110 viathe water intake 162 controlled by an inlet valve 168 (e.g., a solenoidvalve) under control of control unit 112 of water purifier 110. Aconductivity cell 170 a located downstream of the inlet valve 168 alongthe flow path monitors the incoming water conductivity. Incoming waterthen passes a constant flow valve 172, which produces a steady flow ofwater into a reservoir or tank 174 providing that the water pressure isabove a minimum pressure for constant flow valve 172.

Low and high-level switches 178 a and 178 b provided in reservoir ortank 174 detect its water level, while a computer program run on acontrol unit 112 of water purified 110 controls the opening and closedof inlet valve 168, which is open during the filling of tank 174, andclosed when the water level in reservoir 174 activates its high-levelswitch 178 b connected to control unit 112. Inlet valve 168 opens againwhen the water level falls below low-level switch 178 a of reservoir174, tripping the low-level switch connected to control unit 112. If thewater level in the reservoir 174 rises too high, excess water is drainedvia a tank air vent 176 (overflow connection) to drain 116.

Water purifier 110 includes a reverse osmosis (“RO”) pump 140. Controlunit 112 causes pump 140 to stop if low level switch 178 a in reservoir174 detects air or a critically low water level. RO pump 140 providesthe water flow and pressure requisite for the reverse osmosis processtaking place at reverse osmosis module 166. Reverse osmosis module 166filters water as is known to provide purified water at its purifiedwater exit 180 a. Reject water leaving reverse osmosis module 166 at asecond exit 180 b may be fed back into RO pump 140 to conserve waterconsumption or alternatively be pumped to drain 116.

Purified water leaving the RO module 166 passes any one or more of aflow meter 182, a heater 184 a, and a first temperature sensor 186 a. Anadditional conductivity cell 170 b monitors the conductivity of purifiedwater leaving reverse osmosis module 166. The purified water leaveswater purifier 110 through a purified water outlet and flows to PDcycler 20 via a (purified) water line 64 shown also in FIG. 8. Pressureregulator 130 as discussed above is positioned at the purified wateroutlet upstream of water line 64 for regulating fluid pressure in thewater line 64 downstream from pressure regulator 130.

Excess purified water, not used at cycler 20, returns to reservoir 174via a recirculation line 188 provided with a one-way or check valve 280that prevents water in reservoir 174 from flowing through recirculationline 188 into water line 64. In recirculation line 188, the purifiedwater may also pass a second temperature sensor 186 b before re-enteringreservoir 174.

A portion of the rejected water leaving the RO module 166 via line 180 bpasses an auxiliary constant flow valve 190, which provides a steadyflow of rejected water to a three-way valve 192 a (e.g. a three-waysolenoid valve) under control of control unit 112. A remaining portionof the rejected water returns to RO pump 140 via a valve 194 (e.g., amanual needle valve). Three-way valve 192 a selectively diverts therejected water either to drain 116 or back to reservoir 174. Beforereaching reservoir 174, the rejected water may also pass one or more ofa flow indicator 196, an additional heater 184 b and a third temperaturesensor 186 c. All meters and sensors described in connection with waterpurifier 110 in FIG. 16 send their corresponding signals to control unit112 in one embodiment.

Referring again to FIG. 8, system 10 d in one embodiment includes acontainer 198 containing a microbiological growth inhibiting agent. Asillustrated, container 198 is in fluid communication with water purifier110 and/or cycler 20. In FIG. 8, line 272 connects container 198 topurifying circuit 164 (FIG. 16) of water purifier 110. Alternatively,container 198 may be connected via a line (not illustrated) leadingdirectly to disposable cassette 42 operating with cycler 20, or beconnected to water line 64, or be connected to drain line 56.

The agent inhibiting microbiological growth in the container 198 may bea suitable physiologically safe acid, such as citric acid, citrate,lactic acid, acetic acid, or hydrochloric acid (or a combinationthereof). In one the preferred embodiment, container 198 contains citricacid, citrate or a derivative thereof. It is noted that container 198may also include additives provided together with the acid (such as withcitric acid).

Water purifier 110 shown in FIG. 16 may accordingly also include adisinfection circuit. Here, water purifier 110 presents a chemicalintake 274, located for example at the front of purifier 110. When anexternal source of cleaning or disinfection solution (e.g., container198) is connected to the chemical intake 274, a presence sensor 276(e.g. an optical sensor) senses the external source connection. Athree-way valve 192 b under control of control unit 112 at chemicalintake 274 opens towards a chemical intake pump 274 a and reservoir 174.The chemical intake pump 274 a feeds disinfecting solution intoreservoir 174. Optical sensor 276 detects if the source of cleaning ordisinfection solution is connected or disconnected. If/when the sourceis removed or is not detected by sensor 276, the chemical intake pump274 a is stopped or not activated and three-way valve 192 b is closedtowards the chemical intake 274 and instead allows for recirculationfrom reservoir 174, through valve 192 b, back to the reservoir 174.Three-way valve 192 a under control of control unit 112 may also be usedto recirculate water and disinfectant from and to reservoir 174 duringthe phases of chemical disinfection, cleaning and/or rinse.

In a more detailed disinfection phase example, when chemicaldisinfection is initiated, the level in reservoir 174 is adjusted to alevel just above low-level switch 178 a. Control unit 112 causes RO pump140 to start and run until empty level switch 178 a indicates a presenceof air. RO pump 140 is then stopped and inlet valve 168 is opened. Valve168 is maintained open until empty level switch 178 a indicates water.Chemical intake pump 274 a is then run until a preset amount of chemicalsolution is metered into reservoir 174. When the level in reservoir 174reaches high-level switch 178 b via the intake of disinfectant,three-way valve 192 a is opened to drain 116. RO pump 140 circulates thefluid in the flow path during the chemical intake phase and may beoperated in two directions to create turbulent flow and to increasedisinfection time and contact. At the end of the intake phase, bypassvalve 278 is opened and the three-way valve 192 a is actuated to openline 114 to drain 116 and to drain the water level in reservoir 174 toits low-level at switch 178 a.

When the disinfection source (e.g., container 198 in FIG. 8) is removed,reservoir 174 is filled with water to high-level switch 178 b, bypassvalve 278 is closed and three-way valve 192 a is closed in eachdirection. Control unit 112 then causes RO pump 140 to begin circulationthrough the RO module 166, while chemical intake pump 274 a begins thecirculation through chemical intake unit 274, while return overflowvalve 280 is opened. Control unit 112 causes the circulation in the flowpath to continue for a preset amount of time. The speed of RO pump 140is then reduced, bypass valve 278 is opened and the three-way valve 192a is opened to drain 116. Control unit 112 causes both valves 192 a and278 to be deactivated and both pumps 140 and 274 a to be stopped whenthe fluid level falls below low-level switch 178 a.

Purifying circuit 164 in FIG. 16, including the disinfection componentsjust described, may be enclosed inside of a single water purificationcabinet 110 a. As mentioned above, purified water is sent from waterpurifier 110 to disposable set 40 (FIG. 8) via water line 64. Referringagain to FIG. 8, water line 64 feeds purified water to a water port 282of cassette 42 of disposable set 40. Water line 64 is in one embodimenta flexible tube having a first end 64 c connected to an exit of thepurifying circuit 164 of the water purifier 110 (FIG. 16) and a secondend 64 d connected to the water port 282 of the cycler 20. Water line 64may be at least 2 meters long and in one embodiment longer than 4meters. Water line 64 allows water purifier 110 to be installed in aroom having an available water source, while cycler 20 resides in adifferent room in which the patient resides, e.g., sleeps. Water tube 64may accordingly be as long as necessary to connect water purifier 110 tocycler 20.

FIG. 8 also illustrates that system 10 d includes a drain line 56configuration to conduct fluid, such as used dialysis fluid, to a drain,for example drain 116 of water purifier 110. Drain line 56 may be a tubehaving a first end 56 a connected to cassette 42 of cycler 20 and asecond end 56 b connected to purifying circuit 164 of the water purifier110. Drain line 56 may also be a flexible tube, which may be more than 2meters long and in one embodiment longer than 4 meters. Drain line 56may be as long as necessary to connect between water purifier 110 andcycler 20. Water line 64 and drain line 56 in the illustrated embodimentrun parallel using dual lumen tubing. It is also possible that waterpurifier 110 and PD cycler 20 are close together, such that the same twoline fluid path including water line 64 and drain line 56 may forexample be less than 0.5 meters. Moreover, while a dual lumen water line64 and the drain line 56 are illustrated, it is possible that water line64 and drain line 56 are separate.

In the illustrated embodiment of FIG. 8, water line 64 and drain line 56are in direct fluid communication with one another. In particular, theirrespective ends 64 d and 56 a are connected to water port 282 of thecassette 42. Drain line 56 and the water line 64 accordingly bothfluidly communicate with cycler 20 via water port 282. Drain line 56 inthe illustrated embodiment is a tube having one end 56 a connected toend 64 d of water line 64. Again, water line 64 and drain line 56 may bemade from a single dual lumen piece.

Referring to FIGS. 8, 11 and 12, water line 64 (FIG. 11) includes afirst tract 65 a and a second tract 65 b connected to the first tractvia a connector 284. Second tract 65 b is connected to said water port282 and may present a first sterile sterilizing grade filter 70 a. Inthe illustrated embodiment, second tract 65 b is permanently orremoveably connected to cassette 42 and thus a disposable part. In theillustrated embodiment, water line 64 may include a second redundantsterile sterilizing grade filter 70 b placed in series with firststerile sterilizing grade filter 70 a, for example positioned in thesame disposable second tract 65 b connected to cassette 42.

Sterile sterilizing grade filters 70 a and 70 b are disposable in oneembodiment. Sterile sterilizing grade filters 70 a and 70 b may be lessthan 0.1 micron filters that create WFPD from the already highlypurified water exiting water purifier 110. Suitable sterile sterilizinggrade filter 70 a and 70 b are specified herein.

As illustrated in FIG. 11, the drain line 56 may include a first draintract 57 a and a second drain tract 57 b connected to the first draintract via a connector 284. First drain tract 57 a is connectedpermanently or removeably to water port 282 of cassette 42 and formspart of water line 64. In one embodiment, first drain tract 57 a of thedrain line 56 is connected to second water tract 65 b of the water line64. The first drain tract 57 a of the drain line 56 and the second watertract 65 b of the water line 64 form a loop to connector 284 asillustrated in FIG. 11. FIG. 11 illustrates that the loop starts atconnector 284, runs to a tube portion of water line 64, runs to a tubeportion of drain line 56 and ends at connector 284.

FIG. 10 illustrates that water line 64 and drain line 56 includeterminal connector 284 configured for connecting free ends of therespective lines 64 and 56 to an intake 288 of the purifying circuit 164of the water purifier 110 for disinfection of the water and drain lines.

FIG. 9A illustrates a different embodiment, in which each of the waterline 64 and of the drain line 56 has a separate respective connector 284a, 284 b separated one from the other. FIG. 9B illustrates thatregardless of whether a single connector 284 is used (FIG. 11) orseparate connectors 284 a, 284 b are used (FIG. 9A), respective ends ofwater line 64 and of drain line 56 both connect to or run to water port282 of cassette 42. Cassette 42 defines an internal fluid passagewaycommunicating with port 282 to direct fluid within cassette 42 ofdisposable set 40.

FIG. 8 illustrates that water purifier 110 further includes at least onesensor 132 for detecting a property of a fluid flowing in the water line64 and/or in drain line 56. Sensor 132 may be a conductivity sensor or aconcentration sensor located in the drain line 56, and in one embodimentin the second drain tract 57 b of drain line 56. In the illustratedembodiment, sensor 132 is included in the circuit inside the cabinet 110a (FIG. 16) of water purifier 110. In an alternative embodiment (notshown), sensor 132 may be located at the first end 56 a of drain line56, for instance, at first drain tract 57 a.

Additionally, a second sensor (not illustrated) for detecting a property(e.g., the same property detected by first sensor 132, e.g.conductivity) of the fluid flowing in water line 64 and/or in the drainline 56 may be provided. The second sensor may be a conductivity sensoror a concentration sensor and may or may not be located in series withfirst sensor 132. The second sensor may be positioned in a differentportion of the purifying circuit 164 of water purifier 110. Drainedfluid may for example be directed from time to time to the second sensorto check proper working operation of first sensor 132.

As mentioned above, system 10 d in one embodiment includes twoadditional filtration stages for purified water flowing downstream frompurifying unit 110. In one embodiment, two disposable sterilesterilizing grade filters 70 a and 70 b on the water line 64 may beused. However, alternative configurations may be adopted. FIG. 12illustrates one possible alternative configuration in which a firstdisposable sterile sterilizing grade filter 70 a is still located alongwater line 64, while a second sterile disposable sterile sterilizinggrade filter 70 b is located along a patient line 50, extending fromcassette 42 to patient P.

FIG. 13 illustrates an alternative configuration for water purifier 110in which the water purifier 110 includes at least a first ultrafilter290 a and a second ultrafilter 290 b, which are known to those of skillin the art. Water to be purified passes through the two ultrafilters 290a, 290 b located at the end of purifying circuit 164 so that waterpurifier 110 itself provides WFPD. Ultrafilters 290 a, 290 b are notdaily use disposables like disposable sterile sterilizing grade filters70 a, 70 b but do need to be replaced after a given number of treatmentsor ours of service.

FIG. 14 shows an additional alternative embodiment including at leastone of the above-mentioned ultrafilters 290 a and/or 290 b located inwater purifier 110 in combination with a disposable sterile sterilizinggrade filter 70 a, located along patient line 50. FIG. 14 shows anembodiment including only one ultrafilter 290 a, located in waterpurifier 110 provided in combination with a disposable sterilesterilizing grade filter 70 a located along patient line 50. It shouldbe understood that both ultrafilters 290 a and 290 b may be used insteadin combination with a disposable sterile sterilizing grade filter 70 alocated along patient line 50 (or water line 64). FIG. 15 shows yetanother alternative embodiment including only one ultrafilter 290 alocated in water purifier 110 provided in combination with a disposablesterile sterilizing grade filter 70 a located along water line 64. Othercombinations include one ultrafilter with two sterile sterilizing gradefilters, two ultrafilters with one sterile sterilizing grade filter, andtwo ultrafilters with two sterile sterilizing grade filters.

As illustrated in FIG. 8, system 10 d further includes at least onesource 84 a of a first concentrate placed in fluid communication with afirst inlet concentrate port 294 a (e.g., via concentrate line 76/86) ofdisposable cassette 42. Source 84 a of the first concentrate is providedas a first container, wherein first container 84 a may be used forseveral PD fluid preparation cycles until all of the concentratecontained therein has been used. In one embodiment, first concentrate ofcontainer 84 a contains an appropriate osmotic agent, such as dextrose.In a non-limiting example, the first concentrate includes 50% dextroseat pH between 2 and 3. The volume of the first concentrate may be from 1to 4 liters.

System 10 d further includes at least one source 84 b of a secondconcentrate placed in fluid communication with a second inletconcentrate port 294 b (e.g., concentrate line 78/88) of disposablecassette 42. Source 84 b of the second concentrate may be provided in asecond container, wherein second container 84 b may be used for severalPD fluid preparation cycles until all of the concentrate containedtherein has been used. In one embodiment, the second concentratecontains electrolytes and a buffer agent, for example lactate. In anon-limiting example, the second concentrate includes sodium chloride,calcium chloride, magnesium chloride and sodium lactate at pH higherthan 6. The volume of the second concentrate may be from 0.5 to 4liters.

It is contemplated that two concentrates containers 84 a, 84 b will beused, however, three or more concentrates may be used alternative. Forexample, FIG. 12 shows a source 84 c of a third concentrate placed influid communication with a third inlet concentrate port 294 c of cycler20. Source 84 c of the third concentrate may be provided in a thirdcontainer, wherein third container 84 c may be used for several PD fluidpreparation cycles until all of the concentrate contained therein hasbeen used.

In the case of FIG. 12 in which three concentrates are used, the secondconcentrate may, as an example, include sodium chloride, sodium lactateand sodium bicarbonate, while the third concentrate may, as an example,include other electrolytes, such as calcium and magnesium chloride. Inan alternative embodiments, the fluid in third container 84 c may be adrug, a nutritional supplement, or combinations thereof. Of coursedifferent content for the concentrates may be adopted depending on theneeds of patient P and his/her specific circumstances.

First, second and third concentrates 84 a to 84 c are in one embodimentpre-made and pre-sterilized. It is contemplated however that one or moreor all of containers 84 a to 84 c may include a dry concentrate thatreceives a precise amount of WFPD prior to treatment via water purifier110 pumped through cassette 42 into concentrates 84 a to 84 c.

As discussed above, disposable set 40 includes a disposable cassette 42,one embodiment for which is illustrated in FIG. 9A. Here, disposable set40 includes disposable cassette 42, in combination with plural tubes.Tubing set 40 includes a heater/mixing line 60 emerging from aheater/mixing port 296 a of cassette 42 and terminating at heater/mixingcontainer 62, which is configured for receiving WFPD and mixing it toform dialysis fluid. Heater/mixing container 62 is one embodiment acollapsible bag sized to be positioned on a dedicated tray located atthe top of cycler 20.

Disposable set 40 also includes a portion of the water line 64 and aportion of the drain line 56 both emerging from the water port 282 inFIGS. 9A and 9B and three (or more) line portions emerging from first,second and third concentrate ports 294 a to 294 c. Ports 294 a to 294 care configured for connection to respective concentrate bags. FIG. 9Ashows three line portions for connection to concentrates, while FIGS. 8and 9B illustrate (on the right side of cassette 42) water port 282 andfour additional ports in the cassette, where at least two of the fourparts may be used for connection to concentrates.

Patient line 50 emerges from a patient port 296 b of cassette 42 inFIGS. 9A and 9B. One end of patient line 50 is configured for connectionto a transfer set worn by patient P. An additional line 298 extends fromport 296 c of cassette 42 in FIGS. 9A and 9B. Additional line 298 may beused as an additional drain line, as a sample line, or (as shown in FIG.9A) may have one end connected to the patient line 50 to create adialysis fluid loop. Cassette 42 may be provided with additional fluidlines as needed.

Cassette 42 in FIG. 9B is provided with first and second fluid pumpchambers 44 a, 44 b. Pump chambers 44 a and 44 b are in selective fluidcommunication with ports 282, 294 a to 294 c, and 296 a to 296 c viafluid valve valves 46. Fluid pump chambers 44 a and 44 b and fluid valvechambers 46 are actuated pneumatically in one embodiment.

As illustrated in FIG. 9B, water port 282 (and thereby water line 64 anddrain line 56), and the first, second and third ports 294 a to 294 c(and thereby the above-described concentrates) are selectively fluidlyconnected to common fluid passageways 300 a and 300 b formed in therigid plastic portion of cassette 42. Fluid passageways 300 a and 300 bare also selectively fluidly connected to an inlet or an outlet portside of fluid pump chambers 44 a and 44 b. Patient port 296 b is alsoconnected to first common fluid passageway 300 a.

Heater/mixing port 296 a (and therefore heater/mixing container 62) andadditional port 296 c are in the illustrated embodiment fluidlyconnected to second common fluid passageway 300 b formed in rigidcassette 42. Second common fluid passageway 300 b is in turn in fluidcommunication with the opposite inlet or outlet ports of fluid pumpchambers 44 a and 44 b.

First common fluid passageway 300 a and second common passageway 300 bcommunicate with each other by via fluid pump chambers 44 a and 44 b. Inthe case that main patient line 50 and additional patient orrecirculation line 298 are connected to each other, a furthercommunication path is created between fluid passageways 300 a and 300 b.

FIG. 9B illustrates that fluid valve chambers 46 are provided at thementioned ports and also in fluid passageways 300 a and 300 b to directdialysis fluid to or from fluid pump chambers 44 a and 44 b. Fluid valvechambers 46 are also provided at each of the fluid ports of cassette 42.In general, port valve chambers 46 decide which fluid flows to or fromcassette 42, while fluid valve chambers 46 in passageways 300 a and 300b decide which direction that the fluid flows. Fluid valves chambers 46are actuated pneumatically in one embodiment. Here, positive andnegative pressure acting on the valve chambers 46 (closing and openingthe passages, respectively) allows for the selective changing of fluidflow inside cassette 42 of disposable set 40.

In FIG. 8, cycler 20 receives cassette 42 and its set of tubing. Cycler20 is provided with a control unit 22, including one or more processorand memory programmed to drive respective pneumatic valve actuators(e.g., electrically activated pneumatic solenoid valves) to open orclose each of fluid valve chambers 46 to create desired flow pathsinside cassette 42 of disposable set 40.

Control unit 22 is also programmed to control pneumatic pump actuators,e.g., electrically activated pneumatic variable orifice valves, whichselectively allow positive or negative pneumatic pressure to fluid pumpchambers 44 a and 44 b. The valve and pump chambers are in oneembodiment each covered by a membrane that is under positive andnegative pressure. Positive pressure closes the membrane to occlude flowfor fluid valve chambers 46 and pushes the membrane to expel fluid(WFPD, concentrate or dialysis fluid) for fluid pump chambers 44 a and44 b. Negative pressure opens the membrane to allow flow through fluidvalve chambers 46 and pulls the membrane to draw fluid (WFPD,concentrate or dialysis fluid) for fluid pump chambers 44 a and 44 b.

It should be appreciated that control unit 22 may be programmed suchthat either fluid pump chamber 44 a and 44 b may be used to pump anyfluid to any desired destination. Fluid pump chambers 44 a and 44 b maybe used to pump WFPD into cassette 42 individually or together, and/orback to water purifier 110. Fluid pump chambers 44 a and 44 b may beused alone or together to pump concentrates from containers 84 a and 84b into cassette 42. Fluid pump chambers 44 a and 44 b may be used aloneor together to pump mixed dialysis fluid to any one or more of waterpurifier 110, heating/mixing container 62, patient P or drain 116. Fluidpump chambers 44 a and 44 b may further be used to pump mixed dialysisfluid from heating/mixing container 62 to cassette 42. Each of the aboveoperations is performed under the control of control unit 22 in oneembodiment.

One example treatment setup for system 10 d of the present disclosure isillustrated in the sequence of FIGS. 10 to 12. FIG. 10 shows system 10 dbetween treatments, where water purifier 110 is disconnected from cycler20, while water line 64 and drain line 56 are rolled into connectionwith water purifier 110. In one embodiment, water line 64 and drain line56 are connected to an intake 288 of the purifying circuit 164 to createa properly closed fluid circuit in which disinfectant or hot water maybe circulated during the disinfection of water purifier 110 prior totreatment.

FIG. 11 illustrates an initial setup step in which cycler 20 receivesdisposable set 40 including cassette 42, so that cycler 20 can actuatethe pumping and valve membrane of the cassette. Cassette 42 and itsassociated set of lines is installed into the cycler 20. Cassette 42 isloaded into cycler 20 such that patient P may then be prompted by userinterface 30 of cycler 20, which communicates with control unit 22, toconnect concentrate containers 84 a and 84 b properly to cassette 42. Asillustrated herein, the connectors of concentrate containers 84 a and 84b may be made to be different so that it is ensured that the connectorsare connected to the proper port of cassette 42.

FIG. 12 illustrates a next setup step, wherein interface 30 of cycler 20prompts patient P to disconnect water and drain lines 64, 56 from thewater purifier 110, unroll the water and drain lines, and connect thelines to cassette 42, e.g., by means of common connector 284. Again,water and drain lines 64, 56 are two separate lines, but may be providedas part of a single, dual lumen, tube.

Once the dialysis fluid is properly prepared, and disposable set 40 isproperly primed, user interface 30 of cycler 20 notifies patient P ofsame and prompts patient P to connect to patient line 50 and begintreatment. The fluid circuit formed by disposable set 40 includingcassette 42 may be reused for multiple treatments. In such a case, ondays or for treatments in which the circuit of disposable set 40 isbeing reused, patient P need only wait until dialysis fluid is preparedproperly and circuit of disposable set 40 is primed properly beforereconnection to patient line 50 and the beginning of a new treatment.That is, the above connection steps between cycler 20 and water purifier110 are not needed for reuse treatments. Discussed next is oneembodiment for the online preparation of dialysis fluid.

Fluid Preparation for Alternative System 10 d

Referring again to FIG. 8, fluid preparation begins when water purifier110 feeds purified water to the water line 64. Here, water port 282 isclosed via the appropriate fluid valve/actuator at cassette 42, forcingthe purified water to flow through sterile sterilizing grade filters 70a, 70 b and back through drain line 56 to the drain 116. This step fillsthe dual lumen tube 64, 56 connected to the cassette 42, includingsecond tract 65 b (FIG. 11) of water line 64 and first drain tract 57 aof drain line 56.

In a second step, the water port 282 at cassette 42 is opened via anappropriate fluid valve 46 at cassette 42, allowing WFPD to be pumpedvia fluid pump chambers 44 a and 44 b into cassette 42 and heater/mixingbag 62 to prime same.

Next, concentrate checking is performed. Concentrate 84 a is checkedfirst in one embodiment. Water port 282 is closed and first inlet port294 a for concentrate 84 a is opened at cassette 42. Control unit 22causes pump chambers 44 a and 44 b and associated fluid valve chambers46 of disposable cassette 42 to withdraw a prescribed amount of firstconcentrate from concentrate container 84 a and pump said amount ofconcentrate into cassette 42, filling (at least partly) one of the fluidpump chambers 44 a or 44 b.

Control unit 22 causes first inlet port 294 a to close and water port282 to open. The fluid pump chamber 44 a or 44 b containing the firstamount of concentrate 84 a is actuated so that the first concentrate 84a is forced through water port 282 towards and into drain line 56. Asufficient amount of first concentrate reaches first drain tract 57 aaccordingly.

In a subsequent step, the control unit 22 (controlling all cycler 20steps) drives cycler 20 to withdraw purified water from heater/mixingbag 62, and causes WFPD from heater/mixing bag 62 to be pumped to filland flush first or second fluid pump chamber 44 a or 44 b, and then topush forward the WFPD from the fluid pump chamber to thereby push firstconcentrate 84 a into drain line 56 and to remove first concentratetraces from the pump chamber 44 a or 44 b. First concentrate 84 a isthereby forced through drain line 56 towards and past conductivitysensor 132.

In more detail, control unit 22 is in one embodiment programmed to causecycler 20 to pump first concentrate 84 a into first tract 57 a of thedrain line 56, wherein the first tract is positioned immediatelydownstream of water port 282. Control unit 22 causes cycler 20 to pushfirst concentrate 84 a along drain line 56 via WFPD from heater/mixingbag 62 and simultaneously flush the fluid pump chamber 44 a or 44 b.Water port 282 is then closed. As control unit 112 (including one ormore processor or memory) of water purifier 110 causes the waterpurifier to pump purified water into the water line 64, the purifiedwater from water purifier 110 pushes first concentrate 84 a along drainline 56 to and past sensor 132. A property (e.g., conductivity) of firstconcentrate 84 a is then measured and stored at control unit 112.Control unit 112 forwards the measurement property, e.g., wirelessly, tocontrol unit 22 of cycler 20, which analyzes the measurement to identifyand verify concentrate 84 a.

Subsequent to identification and verification of first concentrate 84 a,a similar procedure is adopted for second concentrate 84 b. Here, secondinlet port 294 b is opened and at least one of pump chambers 44 a and 44b is filled at least partially with second concentrate 84 b. Controlunit 22 causes membrane fluid pump chamber 44 a or 44 b to push secondconcentrate 84 b towards drain line 56 and WFPD from the heater/mixingbag 62 to flush pump chamber 44 a or 44 b and to push second concentrate84 b further along the drain line 56. Water port 282 is closed andpurified water from the water purifier 110 is caused to push secondconcentrate 84 b to and past sensor 132. Second concentrate 84 b ismeasured by sensor 132, stored at control unit 112 of water purifier110, and sent to control unit 22 of cycler 20 to identify and confirmsecond concentrate 84 b.

The identification steps may be optional or additional to personalcontainer identification performed by the user and/or achieved throughdedicated mechanical connectors as discussed herein, which prevent theincorrect connection of a concentrate containers 84 a and 84 b tocassette 42. System 10 d is accordingly now ready for mixing theconcentrates and water to produce PD fluid.

To prepare dialysis fluid in one embodiment, WFPD is pumped toheater/mixing bag 62 from water purifier 110, through sterilesterilizing grade filters 70 a and 70 b, through water port 282 viafluid pump chambers 44 a and 44 b and heater/mixing line 60. A firstfilling action pumps possible residual air present in disposable set 40to heater/mixing bag 62 (or to drain 116). Control unit 22 then causescycler 20 to pump first concentrate into heater/mixing bag 62 via thefirst inlet port 294 a.

Control unit 22 may be programmed to cause cycler 20 to perform one ormore additional mixing action. For example, any of fluid pump chambers44 a or 44 b may be caused to withdraw into the pump chambers someamount of mixed fluid (e.g., made from one or both first and secondconcentrates 84 a, 84 b and WFPD) from heater/mixing bag 62, to sendsuch mixture back to heater/mixing bag 62, and repeat this proceduremultiple times (described herein as a “waffling”).

Additional WFPD is then supplied via water line 64 to heater/mixing bag62 so that fluid pump chambers 44 a and 44 b are rinsed with WFPD, andso that first mixed fluid in pump chambers 44 a and 44 b is pumped toheater/mixing bag 62. Control unit 22 then causes cycler 20 to pumpsecond concentrate 84 b to heater/mixing bag 62 via second inlet port294 b, fluid pump chambers 44 a and 44 b and heater/mixing line 60.

Again, control unit 22 may be programmed to cause cycler 20 to performone or more additional mixing action. For example, any of fluid pumpchambers 44 a or 44 b may be caused to withdraw into the pump chambersome amount of mixed fluid (e.g., fluid comprising the first and thesecond concentrate from the first and second concentrate containers 84a, 84 b and WFPD) from heater/mixing bag 62, pump the mixture back toheater/mixing bag 62, and then repeat this procedure multiple times, toimprove the mixing of the first and second mixed fluids (second“waffling” procedure).

Once the required quantities of first and second concentrates 84 a and84 b have been suppled to the heater/mixing bag 62, control unit 22 inone embodiment starts a first dilution phase. Here, WFPD is added toheater/mixing bag 62 via water purifier 110 to reach about 90 to 95%(for example) of a final desired fluid volume of mixed dialysissolution.

Again, control unit 22 may be programmed to cause cycler 20 to performan additional mixing action. For example, any of fluid pump chambers 44a or 44 b may withdraw into the chambers an amount of diluted secondmixed fluid (e.g., diluted fluid comprising first and secondconcentrates 84 a and 84 b and WFPD from heater/mixing bag 62), pump themixture back to heater/mixing bag 62, and then repeat this proceduremultiple times, to further mix the diluted second mixed fluid (third“waffling”) procedure.

Control unit 22 then causes cycler 20 to verify that the diluted secondmixed fluid has been mixed properly. To check proper mixing in oneembodiment the conductivity of the mixed fluid in heater/mixing bag 62is verified. Control unit 22 causes cycler 20 to actuate one or both offluid pump chambers 44 a or 44 b to withdraw a desired amount of dilutedsecond mixed fluid from heater/mixing bag 62 and direct the fluid intofirst drain tact 57 a via water port 282.

In one embodiment, to not waste mixed treatment fluid, when the dilutedsecond mixed fluid reaches the drain line 56, control unit 22 causeswater port 282 to close and WFPD to be pushed by water purifier 110 inwater line 64 towards drain line 56, thereby forcing the diluted secondmixed fluid to flow past sensor 132 for a fluid property check. Thesensed property measured at sensor 132 is received by control unit 112of water purifier 110 and then sent to control unit 22 of cycler 20,e.g., wirelessly, to be analyzed against a setpoint valve as has beendescribed herein.

Control unit 22 of cycler 20 in an embodiment then runs a seconddilution step to fine tune the treatment solution composition. Here,additional WFPD is added to heater/mixing bag 62 to further dilute themixture. The amount of added WFPD is calculated in one embodiment as afunction of the measured property (e.g. conductivity) of the dilutedsecond mixed fluid. In particular, control unit 22 may be programmed todetermine the amount of additional WFPD as a function of the measuredproperty in combination with the previously filled amount of mixeddialysis fluid (water and first and second concentrates 84 a and 84 b).

Again, control unit 22 may be programmed to cause cycler 20 to performan additional mixing action. For example, any of fluid pump chambers 44a or 44 b may withdraw into the chambers some additionally dilutedsecond mixed fluid (e.g., diluted fluid comprising first and secondconcentrates 84 a, 84 b from the first and second concentrate containers84 a, 84 b and WFPD) from heater/mixing bag 62, push the mixture back toheater/mixing bag 62, and then repeat this procedure multiple times, toimprove the mixing of the additionally diluted second mixed fluid(fourth “waffling” procedure).

Control unit 22 is in one embodiment programmed to check theconductivity of the additionally diluted second mixed fluid to confirmcorrect preparation of the treatment fluid. Here, some additionallydiluted second mixed fluid is withdrawn via cycler 20 pumping actionfrom heater/mixing bag 62 and fed to drain line 56. Water purifier 110then pushes WFPD through water line 64 to in turn push the additionallydiluted second mixed fluid past sensor 132 for a final (e.g.,conductivity or concentration) check. A sensor reading is sent, e.g.,wirelessly, from control unit 112 to control unit 22 and analyzed atcycler 20 as discussed herein to verify the proper mixing of thedialysis fluid for treatment.

System 10 d is now ready for treating a patient according to a doctor orclinician prescribed procedure programmed into control unit 22 via userinterface 30. In one embodiment, patient P is connected to cassette 42,and used dialysis fluid from a prior treatment if present is removedfrom the patient's peritoneal cavity and delivered to drain 116 viadrain line 56. Cycler 20 pumps a prescribed fill volume amount ofon-site prepared dialysis fluid to the patient's peritoneal cavity,which is allowed to dwell within patient P for a preset or variableduration, after which cycler 20 causes fluid pump chambers 44 a and 44 bto pump used dialysis fluid including an amount of ultrafiltrationremoved from patient P to drain 116. The above draining, filling anddwelling steps are repeated one or more time to complete the prescribedtreatment. Once all treatment steps are concluded, patient P isdisconnected from disposable set 40, set 40 is removed from cycler 20and water purifier 110 and discarded in one embodiment.

Disinfection Using Growth Inhibiting Agent

In an alternative embodiment, a procedure for extended life ofdisposable set 40 is performed, and may be used with any of systems 10 ato 10 d and any of their alternative embodiments described herein. Here,semi-disposable set 40 is used with cycler 20 for more than onetreatment. Instead of removing disposable set 40 from cycler 20 andwater purifier 110 after treatment, an agent formulated to inhibitmicrobiological growth is pumped from container 198 (FIG. 8) and dilutedat water purifier 110. The diluted agent is pumped by water purifier 110and/or cycler 20 into semi-disposable set 40, including cassette 42 andthe associated line portions and heater/mixing bag 62 connected to thecassette 42.

The growth inhibiting agent may in one embodiment be or include citricacid, citrate or a derivative thereof, and may be pumped from container198, diluted in a portion of the purifying circuit of water purifier110, and then pushed into semi-disposable set 40, for example via waterline 64. In an alternative embodiment, patient line 50 may be connectedto a port of water purifier 110 to receive the diluted growth inhibitingagent for circulation within semi-disposable set 40.

Further alternatively, growth inhibiting agent container 198 may be indirect fluid communication with semi-disposable set 40, for example, viaa connection from container 198 to patient line 50. Control unit 22 herecauses citric acid or citrate (or other suitable acid with or withoutadditives) to be withdrawn from container 198 and be pumped intocassette 42, lines connected thereto and heater/mixing bag 62.

Control unit 22 is in one embodiment programmed to perform one or moremixing step, e.g., the waffling as described herein, so that the agentinhibiting microbiological growth is diluted with the fluid alreadycontained in the circuit, which may be WFPD. In this manner,semi-disposable set 40 is able to be used for more than one treatmentinstead of being discarded after a single use.

In one embodiment, diluted agent is left to reside in semi-disposableset 40 until the start of preparation for a next treatment. At thebeginning of the next treatment, control unit 22 performs a rinsing stepto remove the diluted growth inhibiting agent from semi-disposable set40, wherein the rinsing may be performed using WFPD from water purifier110 and the sterile sterilizing grade filters 70 a and 70 b.

It should be appreciated that the above-described procedure is not adisinfection procedure; rather, the citric acid, citrate, etc., acts abacteriostatic solution to avoid bacterial growth between treatments andextend the use of cassette 42, associated lines and heater/mixing bag62. It should also be appreciated that if traces of the citric acid orcitrate remain in semi-disposable set 40 even after rinsing, the minoramount will not harm the patient considering that human beings commonlyand safely metabolize citric acid and citrate for example.

Hot Water Disinfection

In an alternative multiple use of disposable set 40 embodiment, whichmay be used with any of systems 10 a to 10 d and any of theiralternative embodiments described herein, the anti-growth inhibitingagent just described is replaced by or enhanced using hot waterdisinfection. Heaters 184 a and 184 b of water purifier 110 (FIG. 16),under control of control unit 112, heat its water to 70° C. for exampleto heat disinfect water purifier 110. This is done on a regular, e.g.,daily or between treatment, basis to disinfect semi-disposable set 40.

In an embodiment, control unit 22 of cycler 20 is programmed to causecycler to perform the waffling sequences described above to push andpull the heated water (possibly including an agent configure to inhibitmicrobiological growth) repeatedly throughout cassette 42 andheater/mixing bag 62, and repeatedly through water line segments 64 aand 64 b. The hot water is also cycled through drain line 56 and patientline 50, e.g., up to a hydrophobic membrane located in patient lineconnector 52. When the hot water disinfection of semi-disposable set 40is completed, the hot water is sent to drain 116 at water purifier 110.Again, the hot water disinfection of semi-disposable set 40 may beperformed with or without the growth inhibiting agent described above.

Alternative to Pneumatic Pumping

Each of systems 10 a to 10 d is illustrated above using pneumaticpumping. In an alternative embodiment, cycler may use one or moreperistaltic pump instead. Peristaltic pumping alone may not be accurateenough to mix WFPD and the concentrates to produce a mixed dialysisfluid properly. It is accordingly contemplated to add a balance chambertype structure downstream from each peristaltic pump to greatly improveaccuracy. The balance chamber includes an internal membrane or sheetthat flexes back and forth due to fluid pressure. The tube from eachperistaltic pump splits into two tube segments, one to each of first andsecond inlets to the balance chamber located on either side of themembrane or sheet. Two corresponding outlet tube segments are connectedto first and second outlets of the balance chamber located on eitherside of the membrane or sheet.

Each of the four tube segments is positioned in a cycler in operableconnection to a separate pinch valve. The pinch valves are sequencedalternatingly and repeatedly to allow WFPD or a concentrate from theperistaltic pump to flow alternatingly to either side of the membrane orsheet of the balance chamber, each time expelling a like volume of WFPDor concentrate out of the balance chamber from the other side of themembrane or sheet. Knowing the volume of each balance chamber stroke andcounting strokes results in an accurate amount of WFPD and one or moreconcentrate being delivered to a heater/mixing chamber.

It is contemplated to provide three peristaltic pumps, including (i) aperistaltic WFPD and concentrate pump for pushing WFPD and concentrateto heater/mixing bag 62, (ii) a peristaltic mixed dialysis fluid pumpfor pushing mixed dialysis fluid from heater/mixing bag 62 to patient P,and (iii) a peristaltic used dialysis fluid pump for pushing useddialysis fluid from patient P to drain 116. Each of the three pumpsoperates with a corresponding downstream balance chamber as described toprovide accurate mixing, accurate fresh dialysis fluid delivery topatient P, and accurate used dialysis fluid removal from patient P,resulting in accurate UF.

The mixing regimes (including waffling using the peristaltic pumpbetween heater/mixing bag 62 and patient P) and dialysis fluid testingusing conductivity sensing as described above for the pneumatic systemsare equally applicable to the alternative peristaltic pump version ofthe point of use dialysis system. Concentrate connectors 80 a/80 b and82 a/82 b illustrated and described above in connection with FIGS. 3A to3D may be used with the peristaltic pump system. Heater/mixing bagconnector 100 illustrated and described above in connection with FIGS.4A to 4G may also be used with the peristaltic pump system.

Cycler/Water Purifier Communication

As discussed above at method 210 of FIG. 5, block 222 describes thatcycler 20 pairs or syncs with water purifier 110. Once wirelesslypaired, cycler 20 may order WFPD as needed from water purifier 110. Asdiscussed above, cycler 20 may specify a quantity and temperature forthe WFPD. Additionally, cycler 20 may specify a maximum WFPD supplypressure. If needed, cycler 20 may also tell water purifier 110 to abortthe previously ordered delivery, e.g., if cycler 20 has experienced analarm that is currently being addressed or if patient P has endedtreatment for whatever reason.

As discussed above, to verify that dialysis fluid has been mixedproperly, a sample or slug may be delivered via drain line 56 to aconductivity sensor 132 located at water purifier 110. In an embodiment,after the sample or slug is delivered to water purifier 110, cycler 20requests from water purifier 110 that conductivity reading(s) fromconductivity sensor 132 be sent to cycler 20. Water purifier 110 sendsthe conductivity reading(s) to cycler in response. In anotherembodiment, after the sample or slug is delivered to water purifier 110,cycler 20 puts itself into a wait mode and looks for the conductivityreading(s) from water purifier 110, which are sent automatically tocycler 20. Here, if the wait mode times out with no conductivityreading(s) having been delivered to cycler 20, the cycler may thenrequest that the conductivity reading(s) be delivered.

As discussed above, in one reuse embodiment heated water is deliveredfrom water purifier 110 to disposable set 40 operated by cycler 20 fordisinfection. In one embodiment, water purifier 110 will not deliver theheated water to disposable set 40 until receiving a “ready for hot waterdisinfection” notice from cycler 20. For example, cycler 20 may want toconfirm that patient P is disconnected from patient line 50, e.g., via apressure check and/or manual confirmation via user interface 30 bypatient P, before sending the “ready for hot water disinfection” noticeto water purifier 110. In another example, cycler 20 may want to confirmthat all fluids, e.g., residual fresh dialysis fluid, used dialysisfluid, concentrates, and/or WFPD have been delivered to drain 116 beforesending the “ready for hot water disinfection notice” to water purifier110.

Conductivity Estimating Algorithms

As discussed above, after the PD fluid is prepared by the cycler 20, asample of the fluid (e.g., a slug of freshly mixed dialysis fluid) ispushed from the cycler 20 to and past conductivity sensor 132 in thewater purifier 110. To reduce the amount of waste, the PD fluid sample(e.g., slug) is preferably pushed to the conductivity sensor 132 usingpure water. For example, the PD fluid slug may be pushed through a drainline 56 that is as long as 10 to 20 meters, which may requiresapproximately 125 to 250 mL of fluid to push the slug past theconductivity sensor 132. Also, the PD fluid slug is preferably precededby pure water from water purifier 110 to ensure that the prepared PDfluid slug is only mixing with pure RO water when passing theconductivity sensor 132. By preceding the PD fluid slug with RO water,the RO water may advantageously flush any residual waste fluid that maybe in the drain line 56, thereby preventing the waste fluid fromdistorting the conductivity measurement at the conductivity sensor 132.The slug may be preceded by a predetermined volume of WFPD to sufficientto ensure that the slug does not mix with waste fluid at the head of thesample. As described above, the water purifier 110 may pump WFPD downthe water line 64 and into the drain line 56 to fully prime the drainline 56. Then, the cycler 20 may pump a slug of prepared PD fluid fromthe heater/mixing bag 62 into the drain line 56. After a sufficient slugvolume has been pumped, the water purifier 110 may then pump enough WFPDto the drain line to ensure that an amount sufficient to reach and passthe conductivity pulse maximum is pumped through the conductivity sensor132.

Due to the water preceding the slug of freshly mixed dialysis fluid,some of the slug (e.g., leading edge or head of the slug) is mixed withthe water preceding it, and therefore, a sufficient amount of samplefluid (e.g., slug) is pushed to the conductivity sensor 132 to ensurethe conductivity reading of the slug reflects the conductivity of themixed PD fluid. Depending on the amount of the sample sent to theconductivity sensor 132, the conductivity signal may or may not reach anasymptotic value 402. For example, smaller samples are less likely togenerate a conductivity signal that reach an asymptotic value 402.

In an example, conductivity measurements, or other measurements toensure the prepared PD fluid is mixed properly, may be made using datafrom the end of the slug pulse (a slug pulse 410 is illustrated in FIG.18). For example, conductivity measurements 404 may use the last fewseconds of the top of the conductivity pulse 410 to ensure that readingsclosest to the asymptotic conductivity value 402 are used. However,conductivity readings are sensitive to air (e.g., air bubbles), whichmay result in a sudden spike (e.g., dip) in the conductivity reading,thereby leading to improper readings such as false positives. Inaccuratereadings may require additional measurements or discarding otherwisegood fluid, which wastes time and concentrate.

By applying the conductivity function as discussed below, much moreconductivity data is used and air bubbles will have less of an effect onthe measurement, thereby advantageously minimizing false positives.Additionally, as further discussed below, using the difference betweenthe unknown asymptotic value 402 and the measurement and by taking thenatural logarithm value of the difference further reduces the effect ofair bubbles on the conductivity measurement and asymptote estimate.Moreover, by using the least mean square fit, the “swing” or spikes indata due to air bubbles will be further reduced, thereby furtherreducing the likelihood of a false positive.

Measured conductivity data may be manipulated to predict the asymptoticvalue without actually reaching the asymptotic value of the conductivitysignal from the sample fluid, thereby advantageously minimizing theamount of PD fluid used to determine the conductivity of the prepared PDfluid and thus reducing waste of PD concentrates. In an exampleembodiment, predicting conductivity may result in a 25% reduction in theamount of prepared PD fluid used for a conductivity reading. Forexample, by predicting conductivity, a smaller sample (e.g., 60 to 70milliliters) may be used. Conversely, without predicting conductivity, alarger sample (e.g., 80 to 100 milliliters) may be required for theconductivity signal to reach an asymptotic value 402. For example, alarge enough sample of prepared PD fluid ensures that the conductivitysignal reaches an asymptotic value 402 for a sufficient period of time,thereby ensuring that the reading is based on a series of readings at ornear the asymptotic value 402, which may minimize the risk that possibleair bubbles within the line compromise the result. Additionally,conductivity data may be manipulated to enhance the conductivityreadings or larger PD fluid samples. In other examples, the insidediameter of a drain tube 56 may be decreased to reduce the volume neededto test the conductivity of the sample fluid.

If there is enough sample fluid such that the conductivity signalstabilizes, a conductivity signal may represent a function similar to(A-1) below, and as illustrated in FIG. 17, where A is the asymptoticvalue 402 and τ is the time constant:

$\begin{matrix}{{y(t)} = {A \cdot \left( {1 - e^{{- \frac{1}{\tau}} \cdot t}} \right)}} & \text{(A-1)}\end{matrix}$

However, if the sample is smaller and does not fully stabilize, thesignal may represent the signal illustrated in FIG. 18. By subtractingthe function y(t) in (A-1) from the asymptotic value A and furthertaking the natural logarithm of the difference gives:

$\begin{matrix}{{\ln\left( {A - {y(t)}} \right)} = {{\ln\left( {A - {A \cdot \left( {1 - e^{{- \frac{1}{\tau}} \cdot t}} \right)}} \right)} = {{{\ln(A)} - {\frac{1}{\tau} \cdot t \cdot {\ln(e)}}} = {{\ln(A)} - {\frac{1}{\tau} \cdot t}}}}} & \text{(A-2)}\end{matrix}$

Thus, (A-2) is a linear expression with a slope represented by −1/τ.Even though the asymptotic value A is unknown, a value can be guessed(called A_(g)) based on the visual representation of the pulse 410 orfrom other information. For example, the guess may be what the expectedconductivity value is (e.g., from a look-up table). By using the guess,the resulting expression becomes:

$\begin{matrix}{{\ln\left( {A_{g} - {y(t)}} \right)} = {{\ln\left( {A_{g} - {A \cdot \left( {1 - e^{{- \frac{1}{\tau}} \cdot t}} \right)}} \right)} = {\ln\left( {\left( {A_{g} - A} \right) + {A \cdot e^{{- \frac{1}{\tau}} \cdot t}}} \right)}}} & \text{(A-3)}\end{matrix}$

When A_(g)=A, the resulting expression in (A-3) will become linear.However, when the guess for A_(g) does not equal A, and thus does notequal the true asymptotic value 402, the resulting expression of (A-3)is no longer linear. For example, plotted values where guesses for A_(g)are greater than or less than the asymptotic value are represented inFIG. 19.

In order to estimate the asymptotic value 402, several guesses may beused to determine which guessed asymptotic value gives a straight, orthe straightest line. Once a guess value (A_(g)) is selected, themeasured conductivity data is subtracted from the guess value (A_(g))and the natural logarithm of the difference is calculated. Then, todetermine how “straight” the obtained result is when plotted againsttime, a least mean square fit to the data may be conducted. An absolutedifference between the least mean square line and the test function maybe created and the sum of the absolute differences may be calculated.The guess value (A_(g)) that results in the lowest sum value is thestraightest line, and thus the best predicted conductivity value (e.g.,the predicted asymptotic value that most closely represents theasymptotic value had more sample fluid been pushed past the conductivitysensor 132).

Guesses may be chosen using several different techniques. Additionally,guesses may be based on conductivity data that is measured from the slug(e.g., conductivity measurements 404) or based on expected conductivitydata (e.g., from a look-up table). In one embodiment, an initial guess(A_(g)) may be selected from what the expected conductivity is. Then,subsequent guesses may alternate on opposite sides of the initial guess,until the sum value from the least mean square fit produces a largernumber on both sides of the initial guess (e.g., thereby indicating thatthe guess is worse than the previous guess), which gives one or moredifferent intervals or “valleys” where the best guess fits. For example,if the expected conductivity is 11.64 mS/cm, the initial guess(A_(g)=11.64) may be used and the sum value from the least mean squarefit may be calculated. Then, guesses on opposite sides of the initialguess (e.g., A_(g)>11.64 and A_(g)<11.64) may be used until the sumvalue from the least mean square fit stops producing smaller sums. Forexample, guesses of 11.65, 11.63, 11.66, 11.62, 11.67, etc. may be useduntil a minimum value of the sum from the least mean square fit isdetermined. For example, the smallest sum from the initial guesses maybe 11.67 where guesses using A_(g)=11.66 and A_(g)=11.68 both producedlarger sums. Then, the asymptotic value is somewhere between 11.66 and11.68, and as discussed in more detail below, guesses may be refinedwithin that range using smaller step sizes.

Guesses may be made using various predetermined increments. For example,each iterative guess may be stepped by 0.1, 0.01, 0.001, etc. In otherexamples, larger increments may be used until the two or three bestguesses have been determined. Then, smaller incremental guesses may beused between those guesses. For example, if incremental guesses of11.66, 11.67, and 11.68 (e.g., using 0.01 as a step) produce the threelowest sums from the least mean square fit described above, then guessesbetween 11.66 and 11.68 may be used to refine the guess using a step of0.001, which may advantageously cut down on processing time by reducingthe amount of calculations by control unit 112 of water purifier 110.For example, if the control unit 112 runs all calculations using aninitial of step size of 0.001, then many more iterations may be requiredbefore estimating the best asymptotic value.

In another example, the maximum value 408 of the measured pulse may beused as a starting point for the initial guess. For example, if themaximum value 408 of the pulse is measured as 11.612 mS/cm, 11.612 maybe used as an initial guess. As mentioned above, to avoid imaginarynumbers, an initial guess above the maximum value may be used. Forexample, a range of guesses may be used between a lower end guess (e.g.,maximum measured conductivity value) and an upper end guess (e.g.,expected value of conductivity plus a safety factor) that takes intoaccount that the fluid may be mixed incorrectly. For example, if theexpected conductivity value is 11.64 mS/cm, upper and lower end guessesmay be:

11.612+0.0001<A_(g)<11.612+2·(11.64−(11.612+0.001))

Then, guesses may be stepped from the lower end guess of 11.613 to thehigher end guess of 12.613 in a predetermined step interval, such as0.001. After the sum of the absolute difference of the curve to theirrespective least mean square fit, the lowest sum of the absolutedifference results in the estimate asymptotic value of the conductivity.

Temperature Estimating Algorithm

Similar to the conductivity measurement, the temperature of the fluidsample may also be estimated. Conductivity is dependent on temperatureand the conductivity reading may need to be temperature compensated tobe comparable to other conductivity readings. For example, conductivityreadings may be normalized to 25° C. such that multiple readings may beaccurately compared to each other and also compared to appropriatevalues in a look-up table.

Temperature at conductivity sensor 132 a used for measuring the preparedPD fluid may not be constant. For example, water sent from theaccumulator bag 66 to the drain and prepared PD fluid may have differenttemperatures, such as 18° C. to 25° C. and 37° C. respectively. Thewater from the accumulator bag 66 may be affected by the roomtemperature and/or environment where the system is positioned.

Similar techniques as discussed above with reference to conductivity maybe used to estimate the asymptotic value 412 of the temperature for thefluid sample of the prepared PD fluid. A temperature pulse 420,illustrated in FIG. 20, represents temperature measurements in whichwater from an accumulator bag 66 is followed by a sufficiently largeamount of the prepared PD fluid, such that the temperature reaches anasymptotic value 412.

The temperature pulse 420 may be described by the following function:

$\begin{matrix}{{T(t)} = {T_{0} + {\left( {T_{A} - T_{0}} \right) \cdot \left( {1 - e^{{- \frac{1}{\tau}} \cdot t}} \right)}}} & \text{(B-1)}\end{matrix}$

In expression (B-1), T₀ is the initial temperature, T_(A) is theasymptotic temperature, and τ is the time constant. By subtracting thefunction T(t) in (B-1) from the asymptotic value T_(A) gives:

$\begin{matrix}{{T_{A} - {T(t)}} = {{T_{A} - \left( {T_{0} + {\left( {T_{A} - T_{0}} \right) \cdot \left( {1 - e^{{- \frac{1}{\tau}} \cdot t}} \right)}} \right)} = {\left( {T_{A} - T_{0}} \right) \cdot e^{{- \frac{1}{\tau}} \cdot t}}}} & \text{(B-2)}\end{matrix}$

Taking the natural logarithm of the difference in (B-2) gives:

$\begin{matrix}{{\ln\left( {T_{A} - {T(t)}} \right)} = {{\ln\left( {T_{A} - T_{0}} \right)} - {\frac{1}{\tau} \cdot t}}} & \text{(B-3)}\end{matrix}$

The resulting expression (B-3) is linear expression with a sloperepresented by −1/τ. Similar to the techniques discussed above withrespect to the conductivity value, the temperature value T_(A) may beestimated by using several different guess temperature values until thelowest sum value of the least mean squares line is obtained.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

1. A peritoneal dialysis system comprising: a water purifier including awater outlet connector, a water recirculation connector, and an internalrecirculation loop from the water outlet connector to the waterrecirculation connector; a cycler; and a disposable set operable withthe cycler, the disposable set including a pumping cassette including awater inlet port, a water line in fluid communication with the waterinlet port and the water outlet connector, the water line including atleast one sterile sterilizing grade filter, and a recirculation line influid communication with the water line downstream from the sterilesterilizing grade filter and the water recirculation connector, whereinthe recirculation line and the internal recirculation loop absorbpressure upon a failure of the at least one sterile sterilizing gradefilter.
 2. The peritoneal dialysis system of claim 1, wherein thedisposable set further includes a heater/mixing container in fluidcommunication with the pumping cassette.
 3. The peritoneal dialysissystem of claim 1, wherein the water purifier is configured to enter analarm state upon sensing a change in operating pressure due to thefailure of the at least one sterile sterilizing grade filter.
 4. Theperitoneal dialysis system of claim 3, wherein the recirculation lineand the internal recirculation loop provide time for the water purifierto react to the change in operating pressure.
 5. The peritoneal dialysissystem of claim 1, which includes a pump in operable communication withthe internal recirculation loop.
 6. A disposable set for operation withfirst and second concentrate containers in fluid communication withfirst and second concentrate container connectors, the disposable setcomprising: a pumping cassette including a patient line port, a drainline port, a water inlet port, a heater/mixing port, a first concentrateport, and a second concentrate port; a patient line in fluidcommunication with the patient line port; a drain line in fluidcommunication with the drain line port; a water line in fluidcommunication with the water line port; a heater/mixing container influid communication with the heater/mixing port; a first concentrateline in fluid communication with the first concentrate port, the firstconcentrate line terminating at a first concentrate line connectorhaving a first configuration for mating with the first concentratecontainer connector; and a second concentrate line in fluidcommunication with the second concentrate port, the second concentrateline terminating at a second concentrate line connector having a second,different configuration for mating with the second concentrate containerconnector, such that (i) the first concentrate line connector cannotmate with the second concentrate container connector, and (ii) thesecond concentrate line connector cannot mate with the first concentratecontainer connector.
 7. The disposable set of claim 6, wherein the firstconfiguration and the second configuration have different thread sizes.8. The disposable set of claim 7, wherein the first configurationincludes one of the first concentrate line connector or the firstconcentrate container connector having a first shroud differentialbetween an end of a first shroud and an end of a first male luer port.9. The disposable set of claim 8, wherein the second configurationincludes one of the second concentrate line connector or the secondconcentrate container connector having a second shroud differentialbetween an end of a second shroud and an end of a second male luer port.10. The disposable set of claim 9, wherein the second shrouddifferential is different than the first shroud differential.
 11. Thedisposable set of claim 6, wherein a distal end of the patient lineincludes a patient line connector having a third configuration formating with a patient transfer set.
 12. The disposable set of claim 11,wherein the third configuration is different than the first and secondconfigurations.
 13. The disposable set of claim 6, wherein a distal endof the drain line includes a drain line connector having a thirdconfiguration for mating with a mating connector.
 14. The disposable setof claim 13, wherein the third configuration is different than the firstand second configurations.
 15. The disposable set of claim 13, wherein adistal end of the water line includes a water line connector configuredto mate with the drain line connector.
 16. The disposable set of claim6, wherein a distal end of the water line includes a water lineconnector having a third configuration for mating with a water purifier.17. The disposable set of claim 16, wherein the third configuration isdifferent than the first and second configurations.
 18. A peritonealdialysis system comprising: an accumulator container or bag; a firstfluid system fluidly connected to the accumulator container or bagupstream of the accumulator container or bag, wherein the first fluidsystem is configured to operate such that fluid delivered from the firstfluid system to the accumulator container or bag is at a first pressure;and a second fluid system fluidly connected to the accumulator containeror bag downstream of the accumulator container or bag, wherein thesecond fluid system is configured to operate such that fluid pulled fromthe accumulator container or bag to the second fluid system is at asecond pressure, wherein the first pressure is greater than the secondpressure, and wherein the accumulator container or bag collecting fluidat the first pressure from the first fluid system and dispensing thecollected fluid at the second pressure to the second fluid systemthereby isolates operation of the first fluid system from operation ofthe second fluid system.
 19. The system of claim 18, wherein the secondfluid system includes a cycler.
 20. The system of claim 18, wherein thefirst fluid system includes a water purifier.